Human immunodeficiency virus type 1 envelope epitope-specific CD4(+) T lymphocytes in simian/human immunodeficiency virus-infected and vaccinated rhesus monkeys detected using a peptide-major histocompatibility complex class II tetramer

A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide complex was used to quantitate human immunodeficiency virus type 1 (HIV-1) envelope (Env)-specific CD4(+) T cells in vaccinated and in simian/human immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) were employed to construct this tetrameric complex. A p46-specific proliferative response was seen in sorted, tetramer-binding, but not nonbinding, CD4(+) T cells, directly demonstrating that this response was mediated by the epitope-specific lymphocytes. Although staining of whole blood from 10 SHIV-infected Mamu-DR*W201(+) rhesus monkeys failed to demonstrate tetramer-binding CD4(+) T cells (<0.02%), p46-stimulated peripheral blood mononuclear cells (PBMCs) from 9 of these 10 monkeys had detectable p46 tetramer-binding cells, comprising 0.5 to 15.2% of the CD4(+) T cells. p46-stimulated PBMCs from 7 of 10 Mamu-DR*W201(+) monkeys vaccinated with a recombinant canarypox virus-HIV-1 env construct also demonstrated p46 tetramer-binding cells, comprising 0.9 to 7.2% of the CD4(+) T cells. Thus, Env p46-specific CD4(+) T cells can be detected by tetrameric Mamu-DR*W201-p46 complex staining of PBMCs in both SHIV-infected and vaccinated rhesus monkeys. These epitope-specific cell populations appear to be present in peripheral blood at a very low frequency.     

Effects of dietary caloric restriction and aging on thyroid hormones of rhesus monkeys.

Plasma levels of thyroid hormones - triiodothyronine (T 3 ), thyroxin (T 4 ), and thyroid-stimulating hormone (TSH) were measured in male and female rhesus monkeys (Macaca mulatta) fed either ad libitum or a 30 % calorie-restricted (CR) diet (males for 11 years; females for 6 years). The same hormones were measured in another group of young male rhesus monkeys during adaptation to the 30 % CR regimen. Both long- and shorter-term CR diet lowered total T 3 in plasma of the monkeys. The effect appeared to be greater in younger monkeys than in older counterparts. No effects of CR diet were detected for either free or total T 4, although unlike T 3, levels of this hormone decreased with age. TSH levels also decreased with age, and were increased by long-term CR diet in older monkeys only. No consistent effects of shorter-term CR diet were observed for TSH. In the light of the effects of the thyroid axis on overall metabolism, these results suggest a possible mechanism by which CR diets may elicit their well-known beneficial 'anti-aging' effects in mammals.     

A genetic system for rhesus monkey rhadinovirus: use of recombinant virus to quantitate antibody-mediated neutralization

Rhesus monkey rhadinovirus (RRV), a simian gamma-2 herpesvirus closely related to the Kaposi sarcoma-associated herpesvirus, replicates lytically in cultured rhesus monkey fibroblasts and establishes persistence in B cells. Overlapping cosmid clones were generated that encompass the entire 130-kilobase-pair genome of RRV strain 26-95, including the terminal repeat regions required for its replication. Cloned RRV that was produced by cotransfection of overlapping cosmids spanning the entire RRV26-95 genome replicated with growth kinetics and to titers similar to those of the parental, uncloned, wild-type RRV26-95. Expression cassettes for secreted-engineered alkaline phosphatase (SEAP) and green fluorescent protein (GFP) were inserted upstream of the R1 gene, and the cosmid-based system for RRV genome reconstitution was used to generate replication-competent, recombinant RRV that expressed either the SEAP or GFP reporter gene. Using the SEAP and GFP recombinant RRVs, assays were developed to monitor RRV infection, neutralization, and replication. Heat-inactivated sera from rhesus monkeys that were naturally or experimentally infected with RRV were assayed for their ability to neutralize RRV-SEAP and RRV-GFP infectivity using rhesus monkey fibroblasts. Sera from RRV-positive monkeys, but not RRV-negative monkeys, were consistently able to neutralize RRV infectivity when assayed by the production of SEAP activity or by the ability to express GFP. The neutralizing activity was present in the immunoglobulin fraction. Of the 17 rhesus monkeys tested, sera from rhesus monkey 26-95, i.e., the monkey that yielded the RRV 26-95 isolate, had the highest titer of neutralizing activity against RRV26-95. This cosmid-based genetic system and the reporter virus neutralization assay will facilitate study of the contribution of individual RRV glycoproteins to entry into different cell types, particularly fibroblasts and B cells.     

Effect of age and breeding season on the developmental capacity of oocytes from unstimulated and follicle-stimulating hormone-stimulated rhesus monkeys

Effects of age and season on the developmental capacity of oocytes from unstimulated and FSH-stimulated rhesus monkeys were examined. Immature cumulus-oocyte complexes were matured in vitro in modified CMRL-1066 medium containing 20% bovine calf serum and subjected to in vitro fertilization followed by embryo culture. After fertilization, ova from unstimulated prepubertal monkeys displayed lower development to morula (4%) than those from unstimulated adult females (18% in breeding season and 22% in nonbreeding season). No developmental difference was found between ova from unstimulated adult monkeys in breeding and nonbreeding seasons. However, ova from FSH-primed prepubertal monkeys displayed greater development to blastocyst stage (54%) than those from adult monkeys in the breeding season (16%) and nonbreeding season (0%); and ova from FSH-primed adult females in the breeding season had significantly (P < 0.05) greater developmental competence than those obtained in the nonbreeding season (> or = morula stage, 54% vs. 3%; blastocyst stage, 16% vs. 0%). These data indicate that 1) rhesus monkey oocytes acquire developmental competence in a donor age-dependent manner, and 2) animal age and breeding season modulate the effect of FSH on oocyte developmental competence in the rhesus monkey.     

Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle.

In laboratory rodents, caloric restriction (CR) retards several age-dependent physiological and biochemical changes in skeletal muscle, including increased steady-state levels of oxidative damage to lipids, DNA, and proteins. We used immunogold electron microscopic (EM) techniques with antibodies raised against 4-hydroxy-2-nonenal (HNE) -modified proteins, dinitrophenol, and nitrotyrosine to quantify and localize the age-dependent accrual of oxidative damage in rhesus monkey vastus lateralis skeletal muscle. Using immunogold EM analysis of muscle from rhesus monkeys ranging in age from 2 to 34 years old, a fourfold maximal increase in levels of HNE-modified proteins was observed. Likewise, carbonyl levels increased approximately twofold with aging. Comparing 17- to 23-year-old normally fed to age-matched monkeys subjected to CR for 10 years, levels of HNE-modified proteins, carbonyls, and nitrotyrosine in skeletal muscle from the CR group were significantly less than control group values. Oxidative damage largely localized to myofibrils, with lesser labeling in other subcellular compartments. Accumulation of lipid peroxidation-derived aldehydes, such as malondialdehyde and 4-hydroxy-2-alkenals, and protein carbonyls were measured biochemically and confirmed the morphological data. Our study is the first to quantify morphologically and localize the age-dependent accrual of oxidative damage in mammalian skeletal muscle and to demonstrate that oxidative damage in primates is lowered by CR.     

Nested-PCR检测恒河猴泡沫病毒

目的用nested-PCR检测恒河猴泡沫病毒SFV的前病毒形式。方法从SFV-1的pol区域选择两对引物分别对原代猴肾细胞（rhesus monkey kidney,RMK）及猴外周血淋巴细胞（peripheral blood lymphocytes,PBLs）进行体外扩增,扩增产物经1.0%的琼脂糖凝胶电泳,证实其特异性。阳性对照使用具有典型泡沫样病变的RMK377细胞株的前病毒DNA,阳性对照的PCR扩增产物经测序证实,阴性对照为恒河猴的SRV-1cDNA。结果nested-PCR能快速灵敏的直接从猴外周血淋巴细胞检出SFV的前病毒形式,与RMK细胞培养结果基本相一致。结论本实验所建立的检测SFV的nested-PCR法能快速准确的检测猴群中的SFV的带毒情况,对于提高实验猴的质量具有重要意义。     

Exposure to Sunlight Reduces the Risk of Myopia in Rhesus Monkeys

Exposure to sunlight has recently been postulated as responsible for the effect that more time spent outdoors protects children from myopia, while early life exposure to natural light was reported to be possibly related to onset of myopia during childhood. In this study, we had two aims: to determine whether increasing natural light exposure has a protective effect on hyperopic defocus-induced myopia, and to observe whether early postnatal exposure to natural light causes increased risk of refractive error in adolescence. Eight rhesus monkeys (aged 20-30 days) were treated monocularly with hyperopic-defocus (-3.0D lens) and divided randomly into two groups: AL group (n=4), reared under Artificial (indoor) Lighting (08:00-20:00); and NL group (n=4), exposed to Natural (outdoor) Light for 3 hours per day (11:00-14:00), and to indoor lighting for the rest of the light phase. After being reared with lenses for ca. 190 days, all monkeys were returned to unrestricted vision until the age of 3 years. Another eight age-matched monkeys, reared with unrestricted vision under artificial lighting since birth, were employed as controls. The ocular refraction, corneal curvature and axial dimensions were measured before lens-wearing (at 23±3 days of age), monthly during the light phase, and at the age of puberty (at 1185+3 days of age). During the lens-wearing treatment, infant monkeys in the NL group were more hyperopic than those in the AL group (F=5.726, P=0.032). Furthermore, the two eyes of most NL monkeys remained isometropic, whereas 3 of 4 AL monkeys developed myopic anisometropia more than -2.0D. At adolescence, eyes of AL monkeys showed significant myopic anisometropia compared with eyes of NL monkeys (AL vs NL: -1.66±0.87D vs -0.22±0.44D; P=0.002) and controls (AL vs Control: -1.66±0.87D vs -0.05±0.85D; P<0.0001). All differences in refraction were associated with parallel changes in axial dimensions. Our results suggest that exposure to natural outdoor light might have an effect to reduced hyperopic defocus-induced myopia. Also, the data imply that early life exposure to sunlight may help to maintain normal development of emmetropization later in life, and thus lower the risk of myopic anisometropia in adolescent monkey.     

Estrous behavior of free-ranging rhesus monkeys (Macaca mulatta)

The sexual behavior of a group of free-ranging rhesus monkeys (Macaca mulatta) was studied for 13 consecutive months in an attempt to determine whether or not sexual activity occurred year-round, and the importance of sexual attraction to rhesus monkey social organization.Estrous behavior was seen both inter-menstrually and peri-menstrually, producing a shorter mean estrous cycle length than reported by other workers. New data was gathered on the interrelationships among age, dominance rank, and sexual activity; son-mother and brothersister matings; and sexual favoritism among free-ranging rhesus monkeys.A few females who failed to conceive during the fall breeding season showed cyclic estrous behavior throughout the entire annual cycle. Hypotheses are given as to possible physiological bases for birth season sexual cycles.Several forms of inter-animal bonding, including sexual bonding, are enumerated, and their importance to rhesus monkey social organization discussed.     

Species differences in the aromatization of quinic acid in vivo and the role of gut bacteria

1. The fate of (−)-quinic acid has been investigated in 22 species of animals including man. 2. In man and three species of Old World monkeys, i.e. rhesus monkey, baboon and green monkey, oral quinic acid was extensively aromatized (20–60%) and excreted in the urine as hippuric acid, which was determined fluorimetrically. 3. In three species of New World monkeys, i.e. squirrel monkey, spider monkey and capuchin, in three species of lemurs, i.e. bushbaby, slow loris and tree shrew, in the dog, cat, ferret, rabbit, rat, mouse, guinea pig, hamster, lemming, fruit bat, hedgehog and pigeon, oral quinic acid was not extensively aromatized (0–5%). 4. In the rhesus monkey, injected quinic acid was not aromatized, but largely excreted unchanged. 5. In rhesus monkeys pretreated with neomycin to suppress gut flora, the aromatization of oral quinic acid was considerably suppressed. 6. In rats and rhesus monkeys [¹⁴C]quinic acid was used and this confirmed its low aromatization in rats and its high aromatization in the monkeys. 7. Shikimic acid given orally was excreted as hippuric acid (26–56%) in rhesus monkeys, but not in rats. 8. The results support the view that quinic acid and shikimic acid are aromatized by the gut flora in man and the Old World monkeys.     

Histochemical studies on urate oxidase in several mammals with special reference to uricolytic ability of primates

Summary Strong reactivity for urate oxidase was found in the liver parenchymal cells of the prosimians (i.e. the tree shrew, slow loris, potto and galago) as well as those of lower mammals. The liver parenchymal cells of the platyrrhine monkeys (i.e. the marmoset, owl monkey, squirrel monkey, capuchin monkey and spider monkey) were moderately positive. There was no preferential distribution of granular reaction products in zones of liver lobules of these species. The prosimians and platyrrhine monkeys seem to be uricolytic as lower mammals are. On the other hand, the old world monkeys (i.e. Java monkey and rhesus monkey) and the apes (i.e. the orang-utan and chimpanzee) were histochemically negative.     

Species preference by infant macaques with controlled social experience

In Experiment 1, infant Japanese monkeys and rhesus monkeys were artificially reared in pairs with conspecific or heterospecific monkeys. Preferences of these monkeys for a variety of pictures of Japanese monkeys and rhesus monkeys were repeatedly tested during the first 1 or 2 years of life. The duration of lever-pressing responses to see those pictures was a measure of the preference. All monkeys, Japanese or rhesus, preferred pictures of rhesus monkeys to pictures of Japanese monkeys, without regard to their social experiences. Experiment 2, with an adult Japanese monkey as the subject, and Experiment 3, with different pictures as stimuli, suggested that this preference was not a consequence of any bias in the pictures used. In Experiment 4, a Japanese monkey reared by a rhesus foster mother and rhesus monkeys reared by Japanese monkey mothers received the same preference test. The Japanese monkey infant preferred to see pictures of rhesus monkeys. However, rhesus infants did not show clear species preferences. These results suggest that infants of both Japanese and rhesus monkeys have a native tendency to prefer to see physical characteristics of rhesus monkeys over Japanese monkeys.     

Trypanosoma cruzi: experimental Chagas' disease in rhesus monkeys. II. Ultrastructural and cytochemical studies of peroxidase and acid phosphatase activities

Ultrastructural and cytochemical studies of peroxidase and acid phosphatase were performed in skin, lymph node and heart muscle tissue of rhesus monkeys with experimental Chagas' disease. At the site of inoculation there was a proliferative reaction with the presence of immature macrophages revealed by peroxidase technique. At the lymph node a diffuse inflammatory exudate with mononuclear cells, fibroblasts and immature activated macrophages reproduces the human pattern of acute Chagas' disease inflammatory lesions. The heart muscle cells present different degrees of degenerative alterations and a striking increase in the number of lysosomal profiles that exhibit acid hydrolase reaction product. A strong inflammatory reaction was present due to lymphocytic infiltrate or due to eosinophil granulocytes associated to ruptured cells. The present study provides some experimental evidences that the monkey model could be used as a reliable model to characterize histopathological alterations of the human disease.     

Phylogenetic relationships among Japanese, rhesus, Formosan, and crab- eating monkeys, inferred from restriction-enzyme analysis of mitochondrial DNAs [published erratum appears in Mol Biol Evol 1988 Sep;5(5):601]

Mitochondrial DNA (mtDNA) polymorphisms in four species of macaques, i.e., Japanese monkey (Macaca fuscata), rhesus monkey (M. mulatta), Formosan monkey (M. cyclopis), and crab-eating monkey (M. fascicularis), were analyzed to study phylogenetic relationships. When 17 restriction enzymes of 6-bp recognition were used, 42-49 sites were observed in the samples. The estimated number of nucleotide substitutions per site among Japanese, rhesus, and Formosan monkeys ranges from 0.0318 to 0.0396, and that between the crab-eating monkey and the other monkeys from 0.0577 to 0.0653. These findings suggest that the crab-eating monkey diverged from the other three approximately 1.5-3.0 Myr before the present (Mybp) and that the Japanese, rhesus, and Formosan monkeys diverged approximately 0.9-1.8 Mybp, although the branching order cannot be determined conclusively.      

Polymorphisms of CD3epsilon in cynomolgus and rhesus monkeys and their relevance to anti-CD3 antibodies and immunotoxins

The monoclonal antibody FN18 has been used as a marker for monkey T cells and as a T-cell-depleting reagent when conjugated to diphtheria toxin that was mutated to prevent binding to non-targeted cells. The antibody recognizes a conformational epitope on the ectodomain of monkey CD3epsilon and displays a range of binding activity to the T cells from different rhesus and cynomolgus monkeys. Our quantitative fluorescence-activated cell sorting analysis of the FN18 reactivity to T cells from different rhesus and cynomolgus monkeys showed that there are at least three levels of FN18 reactivity in the monkeys tested: high, moderate and low. On the basis of available DNA sequence information, we determined the gene structure of rhesus CD3epsilon chain and designed primers that can be used to amplify and quickly sequence the ectodomain of monkey CD3epsilon. Our sequence analysis revealed that the extent of nucleotide sequence variation in this area is greater than that previously reported. In addition to the amino acids at positions 45 and 50, we demonstrated that position 35 of CD3epsilon was also important and substitution of amino acid A for V at this position greatly reduced T-cell reactivity to FN18. We found that T cells from monkeys with high FN18 reactivity all had V, E and R at positions 35, 45 and 50 in CD3epsilon, respectively; those having low FN18 reactivity were homozygous in CD3epsilon with at least one of the changes: V35 to A, E45 to G and R to 50Q, whereas members in the moderate group are heterozygous, having both V and A, E and G, R and Q at these locations. A cytotoxicity assay revealed that T cells from a heterozygous rhesus monkey with moderate FN18 reactivity were much (about 40 times) less sensitive to a FN18-derived immunotoxin than those from a homozygous rhesus monkey having high FN18 reactivity.     

Cholesterol metabolism in rhesus monkey, squirrel monkey, and baboon

The metabolism of cholesterol was studied in baboons, rhesus monkeys, and squirrel monkeys while they were being fed either a low fat, low cholesterol (basal) diet or the basal diet supplemented with saturated fat and cholesterol (atherogenic diet). When the diet was changed from basal to atherogenic, the mean total serum cholesterol concentration increased from 70 to 180 mg/dl in the baboon, from 168 to 283 mg/dl in the squirrel monkey, and from 144 to 608 mg/dl in the rhesus monkey. In animals fed the atherogenic diet, the percentage of dietary cholesterol absorbed was greatest in the rhesus monkey and least in the baboon. The fraction of the total body pool of cholesterol that was derived from the diet was greatest in the squirrel monkey and least in the baboon. The turnover of the body pool of cholesterol was several times faster in the squirrel monkey than in the baboon or the rhesus monkey when either dict was fed. The mean total fecal excretion of endogenous cholesterol and bile acid increased in all species on transition to the atherogenic diet; however, the relative contributions of the neutral and acidic fractions to the increase in total excretion differed among species. The difference in percentage of dietary cholesterol absorbed may, in part, account for the large differences in serum cholesterol during the atherogenic diet period. Comparison with other published results indicates that of these species cholesterol metabolism in the baboon is most like that in the human.     

Differences among isolates of simian hemorrhagic fever (SHF) virus

Simian hemorrhagic fever (SHF) virus is a member of the Togaviridae family which currently is unclassified to genus. We have studied the relatedness of four different SHF virus isolates obtained from infected macaque or patas monkeys. Differences were found among isolates in type and severity of disease produced in patas monkeys, cell sensitivity to infection, viral antigens, and levels of specific antibody induced in patas monkeys. Based on these criteria, the four isolates have been grouped in two categories: those producing acute infections in patas monkeys (LVR, P-180) and those producing persistent infections (P-248, P-741). The P-180 isolate induced the most severe disease in experimentally infected patas monkeys, but only occasionally were their infections fatal. Persistently infected patas monkeys were viremic over a period of years, but showed no signs or symptoms of infection. All four isolates were found to be antigenically related by use of enzyme-linked immunosorbent assay (ELISA); the P-248 isolate showing the weakest antigenic relationship. However, none of the four isolates induced cross-neutralizing antibodies in infected patas monkeys. High titers of specific IgG antibody (up to 31,250 as determined by ELISA) were induced in acutely infected patas monkeys (LVR, P-180), but antibody was barely detectable (less than or equal to 50) in persistently infected patas monkeys (P-248, P-741). LVR lytically infected USU-104 cells, patas monkey peritoneal macrophages (PMAC), and rhesus monkey PMAC. The P-180 isolate lytically infected both patas monkey PMAC and rhesus monkey PMAC, but not USU-104 cells. The isolates producing persistent infections (P-248, P-741) lytically infected only rhesus monkey PMAC. These results show that marked differences exist among isolates of SHF virus from naturally infected animals. These differences should be useful in categorizing new isolates.     

X-ray induced translocations in premeiotic germ cells of monkeys

The induction of reciprocal translocations by various X-ray exposures was studied in spermatogonial stem cells of rhesus monkeys (Macaca mulatta) and stump-tailed macaques (Macaca arctoides) by means of spermatocyte analysis many cell generations after irradiation. The yields of translocations recovered from irradiated stump-tailed macaques were lower than those observed in rhesus monkeys and represent in fact the lowest induction rates per Gy ever recorded for experimental mammals. In the rhesus monkey a humped dose-effect relationship was found with (a) a homogeneous response with (pseudo-)linear kinetics below 1 Gy, (b) much more variability at higher doses, and (c) no induction at all at doses of 4 Gy and above. It is suggested that the post-irradiation proliferation differentiation pattern of surviving rhesus monkey spermatogonial stem cells i mainly responsible for these characteristics of the dose-response curve.     

Aging in the musculoskeletal system of rhesus monkeys: I. Passive joint excursion

In order to describe ontogenetic change in the musculoskeletal system of rhesus monkeys, 126 Macaca mulatta from Cayo Santiago, ranging in age from 7 months to 21 years, were examined under anesthesia. Passive joint excursions were measured at the wrist, elbow, shoulder, hip, and knee. Mean ranges of excursion at these joints differed significantly between age groups and by sex. The potential for most movements appeared to decrease approximately 25 degrees over the first two decades of the macaque life span, and males generally showed less potential for movement than females in all age groups. These results are similar to those obtained for humans and are consistent with patterns of positional behavior, trauma, and osteoarthritis observed in this rhesus monkey population. Thus, to fully describe the locomotor strategy of rhesus monkeys, age- and sex-related variation in locomotor anatomy and functional capacity must be considered.     

Xenogeneic immunotherapy of transplantable guinea pig hepatoma with primate leukocyte lysates

Summary Injection of leukocyte lysates prepared from rhesus monkeys xenografted with syngeneic strain-2 guinea pig line 10 hepatoma cells had the ability to increase survival times in guinea pigs receiving lethal, metastasizing doses of the tumor cells. Immunotherapy of the line 10 hepatoma with these xenogeneic anti-line 10 leukocyte lysates resulted in 5 out of 11, or 45.4%, of the animals surviving tumor challenge. Substantially increased survival times were observed in groups of animals treated with lysates from normal or anti-line 1 hepatoma sensitized rhesus monkeys as well. All survivors possessed in vivo skin reactivity and in vitro positive cell-migration inhibition against the line 10 antigen and purified protein derivative. The survivors exhibited negative or marginal immune reactivity against line 1 antigen, strain-2 salt-extracted liver antigen, and a nonspecific antigen, keyhole limpet hemocyanin (KLH). Intact leukocyte lysates from line 10 xenografted baboons, rhesus monkey lysate dialysates, RNA extracts of leukocyte lysates, or lysates of nonlymphoid liver cells obtained from line 10 sensitized rhesus monkeys all failed to extend survival times significantly in strain-2 guinea pigs bearing the line 10 tumor.     

βAmyloid蛋白在恒河猴脑组织中的形态学特点

目的观察βamyloid蛋白在不同年龄的恒河猴脑中的表达及其组织学和细胞超微结构水平的分布特点。方法分别取脑组织额叶、海马、颞叶和顶叶做免疫组化,观察βamyloid蛋白在组织学上的分布特点及与年龄的关系;选用23岁恒河猴一只,灌注后取上述部位做免疫电镜,观察βamyloid蛋白在细胞超微结构水平的分布特点。结果免疫组化染色可观察到年轻猴的神经细胞和胶质细胞中有少量的Aβ40颗粒,以额叶和海马居多。在老年猴脑中Aβ40常聚集成团状斑块。年轻猴脑细胞内未见明显的颗粒状Aβ42,而老年猴的额叶有多量的Aβ42细胞外散在斑块,神经细胞和胶质细胞内也见有Aβ42颗粒状沉积。免疫电镜可观察到Aβ40的胶体金颗粒大部分存在于老年猴神经细胞细胞质中,在细胞间质和小胶质细胞中也可见少量的胶体金颗粒,多见于额叶;标记Aβ42的胶体金颗粒也是多见于神经细胞中,在小胶质细胞中少量存在,同时在颞叶的神经纤维束中也可见Aβ42标记的胶体金颗粒。结论Aβ42是恒河猴老年斑的主要成分,并在其形成过程中起到重要作用。