Regional distribution of adenosine deaminase in the human neuraxis

Adenosine deaminase was determined in 28 different areas of the human neuraxis in 5 adult male cadavers, with no known disease of the nervous system, using a very sensitive colorimetric method. The enzyme was highest in the frontal lobe white matter, and lowest in the medulla and all levels of the spinal cord. Enzyme content was about twice as great in the white matter of the frontal and temporal lobes and cerebellum as it was in the cortical gray matter of these areas, but only slightly higher in the white matter of the parietal and occipital lobes as compared to gray. Average values of the enzyme were found in the remaining areas of the brain, with the exception of the pons and cerebellar white matter, where a higher than average value was noted.     

Clinical Significance of Fronto-Temporal Gray Matter Atrophy in Executive Dysfunction in Patients with Chronic Kidney Disease: The VCOHP Study

Background & Objectives

It is well known that cognitive impairment in patients with chronic kidney disease (CKD) is characterized by executive dysfunction, rather than memory dysfunction, although the precise mechanism of this remains to be elucidated. The purpose of the present study is to examine the correlation between gray matter volume (GMV) and executive function in CKD patients.

Design, Setting, Participants, Measurements

This cross-sectional study recruited 95 patients with non-dialysis-dependent CKD (NDD-CKD) with no history of cerebrovascular disease, who underwent brain magnetic resonance imaging (MRI) and Trail Making Test (TMT) in the VCOHP Study. The subjects underwent brain MRI and TMT part A (TMT-A) and part B (TMT-B). The segmentation algorithm from Statistical Parametric Mapping 8 software was applied to every T1-weighted MRI scan to extract tissue maps corresponding to gray matter, white matter, and cerebrospinal fluid. GMV was normalized by dividing by the total intracranial volume, calculated by adding GMV, white matter volume, and cerebrospinal fluid space volume. Then, normalized whole-brain GMV was divided into four categories of brain lobes; frontal, parietal, temporal, and occipital. We assessed the correlation between normalized GMV and TMT using multivariable regression analysis.

Results

Normalized whole-brain GMV was significantly inversely correlated to the scores of TMT-A, TMT-B, and ΔTMT (TMT-B minus TMT-A). These correlations remained significant even after adjusting for relevant confounding factors. Normalized frontal and temporal GMV, but not parietal and occipital GMV, were significantly inversely correlated with TMT-A, TMT-B, and ΔTMT using multivariable regression analysis.

Conclusions

The present study demonstrates the correlation between normalized GMV, especially in the frontal and temporal lobes, and executive function, suggesting that fronto-temporal gray matter atrophy might contribute to executive dysfunction in NDD-CKD.     

Family Poverty Affects the Rate of Human Infant Brain Growth

Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.     

Phospholipase A2 Activity Is Selectively Decreased in the Striatum of Chronic Cocaine Users

Abstract: Dopamine-mediated stimulation of arachidonic acid metabolism, via activation of the phospholipid metabolizing enzyme phospholipase A₂ (PLA₂), has recently been implicated in dopamine neurotransmitter function. We examined the status of PLA₂ in autopsied brain of 10 chronic users of cocaine, a dopamine reuptake inhibitor. PLA₂ activity, assayed at pH 8.5 in the presence of Ca²⁺, was significantly ( p < 0.01) decreased by 31% in the putamen of cocaine users (n = 10) compared with that in controls (n = 10), whereas activity was normal in the frontal and occipital cortices, subcortical white matter, and cerebellum. In contrast, calcium-independent PLA₂ activity, assayed at pH 7.0, was normal in all brain regions examined. Our finding of altered PLA₂ activity restricted to a region of high dopamine receptor density suggests that modulation of PLA₂ may be involved in mediating some of the dopamine-related behavioral effects of cocaine and could conceivably contribute to dopamine-related processes in the normal brain.     

High-affinity glycine and glutamate transport in pig forebrain white and gray matter: a quantitative study

High-affinity uptake of glycine and glutamate modulates glutamatergic neurotransmission in gray matter. N-Methyl-D-aspartate (NMDA) receptors were recently described on white matter oligodendrocytes, therefore uptake of glutamate and glycine in white matter may also modulate NMDA receptor function. We found that glycine uptake in white structures of pig forebrain (corpus callosum, fimbria, subcortical pyramidal tracts, and occipital subcortical white matter) was similar to that in gray structures (frontal and temporal cortices and hippocampus), and that it was sensitive to sarcosine, a GLYT1 inhibitor (IC(50) 15 microM). Glutamate uptake in white matter was approximately 10% of that in gray; it was sensitive to dihydrokainate, an EAAT2 inhibitor. The levels of glycine and its precursor serine were similar in white and gray matter: approximately 2 and 1 nmol/mg tissue, respectively. The white matter level of glutamate was approximately 7.6 nmol/mg tissue, or approximately 74% of gray matter levels. The activity of serine hydroxymethyl transferase, which converts serine into glycine, was similar in white and gray matter (11-18 pmol/(mg tissue)min), whereas the white matter activity of phosphate-activated glutaminase, which converts glutamine into glutamate, was approximately 100 pmol/(mg tissue)min, or approximately 34% of gray matter activity. The white matter activity of glutamine synthetase, the glial enzyme that converts glutamate into glutamine, was 20-40 nmol/(mg tissue)min in neocortex and 5-6 nmol/(mg tissue)min in white matter. The data show that forebrain white matter is equipped to regulate extracellular levels of glycine and glutamate, functions that may modulate white matter NMDA receptor function.     

Relationship between body mass index and gray matter volume in 1,428 healthy individuals

Objective: To investigate any correlation between BMI and brain gray matter volume, we analyzed 1,428 healthy Japanese subjects by applying volumetric analysis and voxel‐based morphometry (VBM) using brain magnetic resonance (MR) imaging, which enables a global analysis of brain structure without a priori identification of a region of interest. Methods and Procedures: We collected brain MR images from 690 men and 738 women, and their height, weight, and other clinical information. The collected images were automatically normalized into a common standard space for an objective assessment of neuroanatomical correlations in volumetric analysis and VBM with BMI. Results: Volumetric analysis revealed a significant negative correlation in men (P < 0.001, adjusting for age, lifetime alcohol intake, history of hypertension, and diabetes mellitus), although not in women, between BMI and the gray matter ratio, which represents the percentage of gray matter volume in the intracranial volume. VBM revealed that, in men, the regional gray matter volume of the bilateral medial temporal lobes, anterior lobe of the cerebellum, occipital lobe, frontal lobe, precuneus, and midbrain showed significant negative correlations with BMI, while those of the bilateral inferior frontal gyri, posterior lobe of the cerebellum, frontal lobes, temporal lobes, thalami, and caudate heads showed significant positive correlations with BMI. Discussion: Global loss and regional alterations in gray matter volume occur in obese male subjects, suggesting that male subjects with a high BMI are at greater risk for future declines in cognition or other brain functions.     

ESTIMATION OF GLYCOLIPIDS IN FOUR SELECTED LOBES OF HUMAN BRAIN IN NEUROLOGICAL DISEASES1

Glycolipid (ganglioside, cerebroside and cerebroside sulphate) and cholesterol concentrations for cerebral grey matter from frontal, occipital, temporal and hippocampal lobes of patients with neurological diseases (Alzheimer's disease, senile dementia, cerebrocortical atrophy, schizophrenia and chronic alcoholism) and controls are reported. The results indicate that the concentrations of these lipids are not uniform in the different lobes of both diseased and control brains. The concentrations of the cerebrosides and cerebroside sulphates were generally highest in the occipital lobe and lowest in the frontal lobe; ganglioside N-acetymeuraminic acid (NANA) concentrations on the other hand were lowest in the occipital lobe and highest in the frontal lobe. About one-half of the total NANA was found in the lipid-free residues. There was a general decrease in the concentrations of the glycolipids in the grey matter from the frontal, temporal and hippocampal lobes of brain obtained from patients with neurological diseases (the chronic alcoholic being excluded) below the control values from patients with no known neurological diseases. The cholesterol concentrations in the schizophrenic and alcoholic brains were reduced slightly in all the lobes studied. The general decrease in the glycolipid concentration in the diseased brain may indicate the extent of cortical degeneration.     

High-affinity choline uptake and acetylcholine-metabolizing enzymes in CNS white matter. A quantitative study

The presence of nicotinic and muscarinic receptors suggests the occurrence of cholinergic neurotransmission in white matter; however no quantitative information exists on acetylcholine formation and breakdown in white matter. We compared white structures of pig brain (fimbria, corpus callosum, pyramidal tracts, and occipital white matter) to gray structures (temporal, parietal and cerebellar cortices, hippocampus, and caudate) and found that sodium-dependent, high-affinity choline uptake in white structures was 25–31% of that in hippocampus. White matter choline acetyltransferase activity was 10–50% of the hippocampal value; the highest activity was found in fimbria. Acetylcholine esterase activity in white structures was 20–25% of that in hippocampus. The caudate, which is rich in cholinergic interneurons, gave values for all three parameters that were 2.8–4 times higher than in hippocampus. The results suggest a certain capacity for cholinergic neurotransmission in central nervous white matter. The white matter activity of pyruvate dehydrogenase, which provides acetyl-CoA for acetylcholine synthesis, ranged between 33 and 50% of the hippocampal activity; the activity in the caudate was similar to that in hippocampus and the other gray structures, which was true also for other enzymes of glucose metabolism: hexokinase, phosphoglucomutase, and glucose-6-phosphate dehydrogenase. Acetylcholine esterase activity in white matter was inhibited by the nerve agent soman, which may help explain the reported deleterious effect of soman on white matter. Further, this finding suggests that acetylcholine esterase inhibitors used in Alzheimer's disease may have an effect in white matter.     

Topographical Atlas of the Gangliosides of the Adult Human Brain

Forty different brain samples, consisting of neocortical, archicortical, and paleocortical areas; telencephalic, diencephalic, and mesencephalic subcortical nuclei; and the cerebellum as well as some of the corresponding white matter bundles were analyzed with respect to total content of ganglioside-sialic acid and the ganglioside pattern. The total content of gangliosides seems to depend mainly on the proportions of gray and white matter. Thus, neocortical areas, which are rich in gray matter, have a four- to fivefold higher ganglioside content (per milligram of protein) than white matter-rich samples such as optic chiasm, capsula interna, or corpus callosum. White matter-rich regions, although very heterogeneous in ganglioside composition, are further characterized by appreciable amounts of the myelin-enriched GM4. In the neocortex a remarkable degree of regional pattern differences was revealed. In the frontal and parietal areas there is a moderate, and in the temporal region a strong preponderance of sialic acid bound to gangliosides of the a-pathway (GD1a, GM1). In contrast, the occipital cortex favors the b-pathway of ganglioside synthesis (GQ1b, GT1b, GD1b). A predominance of "b-gangliosides" was found in all structures that are related to the visual system (optic chiasm, pulvinar-thalamus, superior colliculi, visual cortex) as well as in the cerebellum and the nucleus ruber. All diencephalic nuclei tend to favor slightly "b-gangliosides," while the mesencephalic nuclei are very heterogeneous in their ganglioside composition. A preponderance of "a-gangliosides" was found in the periamygdalar cortex, putamen, inferior colliculi, substantia nigra, frontal white matter, internal capsule, globus pallidus, basal nucleus of Meynert, and corpus callosum as well as in the frontal, parietal, and temporal cortices. An exceptional predominance of GM1 and GD1a was revealed for the hippocampal archicortex and the amygdala, suggesting a possible functional correlation to glutaminergic synaptic transmission.     

一例艾滋病痴呆综合征病人HIV-1 gp120基因多样性及生物学活性位点分析

为探讨人类免疫缺陷病毒1型HIV-1 gp120基因多样性和生物学活性位点与艾滋病痴呆综合征之间的关系,从一例艾滋病痴呆综合征病例尸检标本的淋巴结和中枢神经组织(大脑5个部位:颞叶灰/白质连接处、脑室周围组织、脉络丛、枕叶白质及枕叶灰/白质连接处)提取不同组织来源的基因组DNA,经PCR法扩增HIV-1 gp120基因,经克隆后挑选阳性克隆菌株,对插入片段进行测序。用生物学软件处理并绘制系统发生树,分析糖基化位点,计算ds/dn值,分析V3顶端四肽及关键位点的氨基酸。结果显示,该病人感染的病毒是HIV-1B亚型;分离自不同组织的HIV-1 gp120基因存在差异;与标准序列相比,分离自该病人的HIV-1 gp120基因的部分生物学活性位点存在改变,且源自外周淋巴组织与中枢神经组织的HIV-1 gp120基因中部分生物学活性位点也存在差异。结果表明,HIV-1 gp120基因多样性及与脑组织相关的某些生物学活性位点的改变可能与艾滋病痴呆综合征的发病机制存在一定关系。     

Brain organization of gorillas reflects species differences in ecology

Gorillas include separate eastern (Gorilla beringei) and western (Gorilla gorilla) African species that diverged from each other approximately 2 million years ago. Although anatomical, genetic, behavioral, and socioecological differences have been noted among gorilla populations, little is known about variation in their brain structure. This study examines neuroanatomical variation between gorilla species using structural neuroimaging. Postmortem magnetic resonance images were obtained of brains from 18 captive western lowland gorillas (Gorilla gorilla gorilla), 15 wild mountain gorillas (Gorilla beringei beringei), and 3 Grauer's gorillas (Gorilla beringei graueri) (both wild and captive). Stereologic methods were used to measure volumes of brain structures, including left and right frontal lobe gray and white matter, temporal lobe gray and white matter, parietal and occipital lobes gray and white matter, insular gray matter, hippocampus, striatum, thalamus, each hemisphere and the vermis of the cerebellum, and the external and extreme capsules together with the claustrum. Among the species differences, the volumes of the hippocampus and cerebellum were significantly larger in G. gorilla than G. beringei. These anatomical differences may relate to divergent ecological adaptations of the two species. Specifically, G. gorilla engages in more arboreal locomotion and thus may rely more on cerebellar circuits. In addition, they tend to eat more fruit and have larger home ranges and consequently might depend more on spatial mapping functions of the hippocampus. Am J Phys Anthropol 156:252–262, 2015. © 2014 Wiley Periodicals, Inc.     

Frontal White Matter Volume Is Associated with Brain Enlargement and Higher Structural Connectivity in Anthropoid Primates

Previous research has indicated the importance of the frontal lobe and its ‘executive’ connections to other brain structures as crucial in explaining primate neocortical adaptations. However, a representative sample of volumetric measurements of frontal connective tissue (white matter) has not been available. In this study, we present new volumetric measurements of white and grey matter in the frontal and non-frontal neocortical lobes from 18 anthropoid species. We analyze this data in the context of existing theories of neocortex, frontal lobe and white versus grey matter hyperscaling. Results indicate that the ‘universal scaling law’ of neocortical white to grey matter applies separately for frontal and non-frontal lobes; that hyperscaling of both neocortex and frontal lobe to rest of brain is mainly due to frontal white matter; and that changes in frontal (but not non-frontal) white matter volume are associated with changes in rest of brain and basal ganglia, a group of subcortical nuclei functionally linked to ‘executive control’. Results suggest a central role for frontal white matter in explaining neocortex and frontal lobe hyperscaling, brain size variation and higher neural structural connectivity in anthropoids.     

White Matter Changes in Patients with Amnestic Mild Cognitive Impairment Detected by Diffusion Tensor Imaging

Compared to normal aging adults, individuals with amnestic mild cognitive impairment (aMCI) have significantly increased risk for progressing into Alzheimer’s disease (AD). Autopsy studies found that most of the brains of aMCI cases showed anatomical features associated with AD pathology. The recent development of non-invasive neuroimaging technique, such as diffusion tensor imaging (DTI), makes it possible to investigate the microstructures of the cerebral white matter in vivo. We hypothesized that disrupted white matter (WM) integrity existed in aMCI. So we used DTI technique, by measuring fractional anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and 28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole-brain FA and MD images in each individual and group comparisons were carried out. Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the association and projection fibers of frontal, parietal, and temporal lobes, corpus callosum, bilateral corona radiation, right posterior thalamic radiation and right sagittal stratum. aMCI patients also showed significantly increased MD widespreadly in the association and projection fibers of frontal, parietal and temporal lobes, and corpus callosum. Assessment of the WM integrity of the frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may aid early diagnosis of aMCI.     

Neurochemical Abnormalities in Brains of Renal Failure Patients Treated by Repeated Hemodialysis

We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.     

Susceptibility-Weighted Imaging Provides Insight into White Matter Damage in Amyotrophic Lateral Sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder, characterised by widespread white matter damage. There is growing evidence that disturbances in iron metabolism contribute to white matter alterations.

Materials & Methods

We analysed the data of susceptibility-weighted imaging (SWI) of white matter in a cohort of 27 patients with ALS and 30 healthy age-matched controls.

Results

Signal alterations were found on SWI in the corpus callosum; along the corticospinal tract (subcortical motor cortex, posterior limb of the internal capsule and brainstem levels) and in the subgyral regions of frontal, parietal, temporal, occipital and limbic lobes. Alterations of white matter in the corpus callosum correlated with disease severity as assessed by the revised ALS functional rating scale.

Conclusion

SWI is capable of indicating iron and myelin disturbances in white matter of ALS patients. The SWI patterns observed in this study suggest that widespread alterations due to iron disturbances occur in patients with ALS and correlate with disease severity.     

High-affinity GABA uptake and GABA-metabolizing enzymes in pig forebrain white matter: a quantitative study

GABA receptor activation in central nervous white matter may be protective during white matter hypoxia in the adult, and it may modify axonal conduction, especially in the developing brain. GABA uptake is important for the shaping of the GABA signal, but quantitative data are lacking for GABA uptake and GABA-metabolizing enzymes in central nervous white matter. We report that high-affinity uptake of GABA in adult pig corpus callosum, fimbria, subcortical pyramidal tracts, and occipital white matter is approximately 20% of that in temporal cortex gray matter. Tiagabine (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures. This finding indicates that GAT-1 is an important GABA transporter in white matter and suggests that white matter GABA uptake is inhibited during tiagabine therapy. GABA transaminase activity in white structures was approximately 20% of neocortical values. Glutamate decarboxylase (GAD) activity in white structures was only 4% of that in neocortex (7-12 pmol/mg tissue x min(-1) versus approximately 200 pmol/mg tissue x min(-1)). Since white matter activity of citrate synthase of the tricarboxylic acid cycle was approximately 25% of neocortical values ( approximately 0.4 nmol/mg tissue x min(-1) versus approximately 1.5 nmol/mg tissue x min(-1)), the low GAD activity suggests a slower metabolic turnover of GABA in white than in gray matter.     

The Role of Aerobic Fitness in Cortical Thickness and Mathematics Achievement in Preadolescent Children

Growing evidence suggests that aerobic fitness benefits the brain and cognition during childhood. The present study is the first to explore cortical brain structure of higher fit and lower fit 9- and 10-year-old children, and how aerobic fitness and cortical thickness relate to academic achievement. We demonstrate that higher fit children (>70th percentile VO_2max) showed decreased gray matter thickness in superior frontal cortex, superior temporal areas, and lateral occipital cortex, coupled with better mathematics achievement, compared to lower fit children (<30th percentile VO_2max). Furthermore, cortical gray matter thinning in anterior and superior frontal areas was associated with superior arithmetic performance. Together, these data add to our knowledge of the biological markers of school achievement, particularly mathematics achievement, and raise the possibility that individual differences in aerobic fitness play an important role in cortical gray matter thinning during brain maturation. The establishment of predictors of academic performance is key to helping educators focus on interventions to maximize learning and success across the lifespan.     

Cortical Thickness and Subcortical Gray Matter Reductions in Neuropsychiatric Systemic Lupus Erythematosus

Within systemic lupus erythematosus (SLE) patients can be divided into groups with and without central nervous system involvement, the latter being subcategorized as neuropsychiatric systemic lupus erythematosus (NPSLE). While a number of research groups have investigated NPSLE, there remains a lack of consistent application of this diagnostic criteria within neuroimaging studies. Previous neuroimaging research suggests that SLE patients have reduced subcortical and regional gray matter volumes when compared to controls, and that these group differences may be driven by SLE patients with neuropsychiatric symptoms. The current study sought to compare measures of cortical thickness and subcortical structure volume between NPSLE, SLE, and healthy controls. We hypothesized that patients with NPSLE (N = 21) would have thinner cortex and reduced subcortical gray matter volumes when compared to SLE (N = 16) and control subjects (N = 21). All subjects underwent MRI examinations on a 1.5 Tesla Siemens Sonata scanner. Anatomical reconstruction and segmentation were performed using the FreeSurfer image analysis suite. Cortical and subcortical volumes were extracted from FreeSurfer and analyzed for group differences, controlling for age. The NPSLE group exhibited decreased cortical thickness in clusters of the left frontal and parietal lobes as well as in the right parietal and occipital lobes compared to control subjects. Compared to the SLE group, the NPSLE group exhibited comparable thinning in clusters of the frontal and temporal lobes. Controlling for age, we found that between group effects for subcortical gray matter structures were significant for the thalamus (F = 3.06, p = .04), caudate nucleus (F = 3.19, p = .03), and putamen (F = 4.82, p = .005). These results clarify previous imaging work identifying cortical atrophy in a mixed SLE and NPSLE group, and suggest that neuroanatomical abnormalities are specific to SLE patients diagnosed with neuropsychiatric symptoms. Future work should help elucidate the underlying mechanisms underlying the emerging neurobiological profile seen in NPSLE, as well as clarify the apparent lack of overlap between cortical thinning and functional activation results and other findings pointing to increased functional activation during cognitive tasks.     

Bovine brain gray and white matter exhibit differential protein prenyl transferase activity

Protein farnesyl transferase and geranylgeranyl transferase-I activities were determined in gray and white matter from various regions of bovine brain. Farnesyl transferase activity was 3–8 times greater than geranylgeranyl transferase-I activity. However, farnesyl transferase activity was about 2 times greater in the white matter than in the gray matter in all regions of the brain. Mixing experiments indicated lack of farnesyl transferase activators in white matter. This difference in farnesyl transferase activity may be due to enzyme content and may have implications in brain cell function.     

Beta-secretase-cleaved amyloid precursor protein in Alzheimer brain: a morphologic study

β-amyloid (Aβ) is the main constituent of senile plaques seen in Alzheimer's disease. Aβ is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases β- and β-secretase. In this study, we examined content and localization of β-secretase-cleaved APP (β-sAPP) in brain tissue sections from the frontal, temporal and occipital lobe. Strong granular β-sAPP staining was found throughout the gray matter of all three areas, while white matter staining was considerably weaker. β-sAPP was found to be localized in astrocytes and in axons. We found the β-sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal β-sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. β-sAPP was also found surrounding senile plaques and cerebral blood vessels. The results presented here show altered β-sAPP staining in the AD brain, suggestive of abnormal processing and transport of APP.