Interactions of 17β-Hydroxysteroid Dehydrogenase Type 10 and Cyclophilin D in Alzheimer's Disease

The nucleus-encoded 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) regulates cyclophilin D (cypD) in the mitochondrial matrix. CypD regulates opening of mitochondrial permeability transition pores. Both mechanisms may be affected by amyloid β peptides accumulated in mitochondria in Alzheimer's disease (AD). In order to clarify changes occurring in brain mitochondria, we evaluated interactions of both mitochondrial proteins in vitro (by surface plasmon resonance biosensor) and detected levels of various complexes of 17β-HSD10 formed in vivo (by sandwich ELISA) in brain mitochondria isolated from the transgenic animal model of AD (homozygous McGill-R-Thy1-APP rats) and in cerebrospinal fluid samples of AD patients. By surface plasmon resonance biosensor, we observed the interaction of 17β-HSD10 and cypD in a direct real-time manner and determined, for the first time, the kinetic parameters of the interaction (k_a 2.0?×?10⁵ M¹s^?1, k_d 5.8?×?10⁴ s^?1, and K_D 3.5?×?10^–10 M). In McGill-R-Thy1-APP rats compared to controls, levels of 17β-HSD10–cypD complexes were decreased and those of total amyloid β increased. Moreover, the levels of 17β-HSD10–cypD complexes were decreased in cerebrospinal fluid of individuals with AD (in mild cognitive impairment as well as dementia stages) or with Frontotemporal lobar degeneration (FTLD) compared to cognitively normal controls (the sensitivity of the complexes to AD dementia was 92.9%, that to FTLD 73.8%, the specificity to AD dementia equaled 91.7% in a comparison with the controls but only 26.2% with FTLD). Our results demonstrate the weakened ability of 17β-HSD10 to regulate cypD in the mitochondrial matrix probably via direct effects of amyloid β. Levels of 17β-HSD10–cypD complexes in cerebrospinal fluid seem to be the very sensitive indicator of mitochondrial dysfunction observed in neurodegeneration but unfortunately not specific to AD pathology. We do not recommend it as the new biomarker of AD.

     

Famous Landmark Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Disease

Background

Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer''s disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored.

Objectives

To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls.

Patients and Methods

A total of 114 patients, 13 with single domain (SD–aMCI) and 30 with multiple domains (MD–aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI.

Results

Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls.

Conclusions

Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD–aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.     

Growth rates of dominant planktonic ciliates in two freshwater bodies of different trophic degree

The in situ growth rates of dominant ciliate species were studiedduring and shortly after phytoplankton peaks in two water bodies:the eutrophic Rímov Reservoir (South Bohemia, Czech Republic)and the oligo-mesotrophic Piburger See (Tyrol, Austria). Growthrate estimates based on changes in ciliate abundances in incubatedpre-screened samples (E_N) were compared with those derived fromthe ciliate cell volume and ambient temperatures (E_T). The valuesof E_N were always rather lower than those of E_T. During thestudies, the food supply limited the ciliate growth dependingon the ciliate feeding mode. An ecological grouping into filterfeeding versus raptorial feeding (‘hunting’) species,on the one hand, and attached/crawling (browsing) versus freeswimming species, on the other hand, clearly affected experimentalestimation. Both fine filter feeders (namely attached) and browsersexhibited a calculated E_N closer to the theoretical (maximum)E_T than did hunters and coarse filter feeders. It was apparent,for example, comparing E_N and E_T (day^–1) of the followingspecies: filter feeders Halteria grandinella (E_N = 0.42; E_T>1.4), Strobilidium hexakinetum (0.34;>1.9), Pelagohalteriaviridis (0.27;>0.9), Vorticella aquadulcis complex (0.75;>1.0);raptorial Balanion planctonicum (0.65;>1.5), Urotricha furcata(in Rímov Reservoir 0.65;>2.1; in Piburger See 0.20;>1.5),Rhabdoaskenasia minima (0.22;>1.0), Askenasia acrostomia(0.12;>0.6); opportunistic Cyrtolophosis mucicola (0.42;>1.6)and Cinetochilum margaritaceum (0.86;>1.4). Predation byrotifers apparently affected measurements in several samplescontaining {small tilde}400 rotifers l^–1 however, it seemedto be of little importance in the water column.