Prior research demonstrated a functional interplay between the FKBP52 immunophilin and tau, with a notable reduction in AD brain neurons correlating with tau accumulation. Furthermore, our findings indicate that FKBP52 co-localizes with autophagy-lysosomal markers and a pathological early tau isoform in AD neurons, suggesting its possible involvement in clearing autophagic tau.Our investigation focused on identifying whether differences in neuronal FKBP52 expression levels and subcellular localization could be observed in AD, PSP, familial FTLD-Tau, the hTau-P301S mouse model, in contrast to controls.Immunohistofluorescence was employed to meticulously examine and quantify FKBP52 in individual cells of postmortem brain tissues from human tauopathies and in the spinal cords of hTau-P301S mice.The neuronal autophagy-lysosomal pathway, in various tauopathies and hTau-P301S mice, showcases a comparable decline in FKBP52 and its re-localization along with early pathological tau forms. We document an early decrease in FKBP52 levels during the pathological progression of Alzheimer's disease, observed in neurons with tau deposits within the minimally involved frontal cortex of Braak IV Alzheimer's brains, and in the spinal cords of asymptomatic one-month-old hTau-P301S mice.The significant contribution of FKBP52 to cellular signaling, and its potential function in the elimination of tau, is supported by our data. This suggests that preventing the decline or restoring the normal level of FKBP52 during the early stages of tauopathies, such as AD, familial FTLD-Tau, and PSP, holds promise as a novel therapeutic strategy.Our research indicates that FKBP52 is essential for cellular signaling and potentially involved in removing tau. Therefore, the prevention of FKBP52 decline or the restoration of its typical expression during the early stages of tauopathies, such as Alzheimer's disease, familial frontotemporal lobar degeneration with tau, and progressive supranuclear palsy, may represent a novel therapeutic direction.Sleep duration and engagement in leisure activities are correlated, and both contribute to cognitive abilities, but most studies have only assessed one of these crucial factors.Analyzing the individual and combined effects of leisure activities and sleep duration on cognitive performance in seniors.A total of 7796 participants, aged 65 years or older, were recruited from the Chinese Longitudinal Healthy Longevity Survey during the 2008-2018 period (waves 5-8). At the commencement of the study, self-reported data were gathered on leisure activities and sleep duration, and repeated cognitive function measurements were made using the Chinese version of the Mini-Mental State Examination (MMSE) both initially and at subsequent follow-up points. Regression coefficients and their 95% confidence intervals were determined using linear mixed models.The follow-up process lasted a median 577 years. After accounting for interdependencies and potential confounders, a lower leisure activity score (each 1-point decrease was associated with -0.033, 95% confidence interval -0.036 to -0.030) and a longer sleep duration (each 1-hour increase was linked to -0.017, 95% confidence interval -0.022 to -0.011) were independently related to a lower MMSE score. In addition, we noted an additive effect of leisure activities on sleep duration, a statistically significant observation (p-interaction<0.0001). Prolonged sleep duration and a low leisure activity score were strongly correlated with a lower MMSE score (=-251, 95% CI -285 to -216) relative to the group with a high leisure activity score and typical sleep patterns.Cognitive function exhibited an association with both sleep duration and leisure activities, separate from each other. In addition, the coupling of insufficient leisure time with prolonged sleep duration anticipated a worsening cognitive state, reflecting the preclinical stage of Alzheimer's disease, demonstrating an additive effect.Cognitive function's association with leisure activities and sleep duration was found to be independent of each other. Compounding the effects, leisure inactivity, when coupled with a prolonged sleep duration, showed an additive relationship with poorer cognitive function, a hallmark of preclinical Alzheimer's disease.One biological manifestation of Alzheimer's disease (AD) is the atrophy of the medial temporal lobe (MTL), which is detectable through magnetic resonance imaging (MRI) segmentation.A longitudinal, multicenter study evaluating the practical clinical applicability of automated volumetry in a pre-dementia cohort, stratified by cognitive status and biomarker profiles.MTL morphometry was determined from MRI scans through the application of the Automatic Segmentation of Hippocampal Subfields (ASHS) procedure. The recently developed longitudinal ComBat was instrumental in harmonizing scanner effects. Subjects, categorized by the A/T/N system, fell into the groups of normal controls (NC), subjective cognitive decline (SCD), or mild cognitive impairment (MCI). The positive or negative values of A, T, and N were ascertained by assessing the A42/40 ratio, phosphorylated tau, and total tau in cerebrospinal fluid. Longitudinal data for 206 of the 406 subjects was collected by stage, and for 212 by the A/T/N criteria.A-/T-/N- individuals possessed larger entorhinal cortex, anterior, and posterior hippocampus volumes at baseline, compared to A+/T+orN+ individuals. Subregions in the MCI A+ group were comparatively smaller in size than those in the NC A- group at baseline. Comparative longitudinal studies indicated significantly greater hippocampal atrophy in the SCD A+ and MCI A+ groups, specifically in the A+/T-/N- and A+/T+orN+ subgroups, in both the anterior and posterior hippocampus when compared to control subjects. Only in MCI A+ subjects, did longitudinal atrophy manifest in the entorhinal and parahippocampal cortices, not observed in NC A- individuals.MTL neurodegeneration, largely consistent with existing models, suggests that harmonized MRI volumetry might prove applicable in typical clinical multi-center cohorts.Our investigation into MTL neurodegeneration yielded results largely consistent with existing models, suggesting the feasibility of harmonized MRI volumetry within the parameters of typical clinical multi-center studies.Studies on Alzheimer's disease (AD) strongly indicate a connection to metabolic dysfunction, highlighting a multifaceted interaction between glucose metabolism, glutamatergic balance, and amyloid plaque formation. Elevated soluble amyloid-A, an early marker of Alzheimer's disease-associated cognitive decline, contributes to concurrent disruptions in glutamatergic and metabolic equilibrium in human and male transgenic AD models. Undoubtedly, the precise consequences of focusing on the primary time-sensitive targeting of hippocampal glutamatergic activity on glucose regulation in a mouse model displaying amyloidogenic tendencies are yet to be elucidated. Past investigations exhibited increased glucose uptake and metabolic activities using a neuroprotective glutamate modulator (riluzole), reinforcing the connection between glucose and glutamatergic balance.We surmised that targeting early glutamatergic hyperexcitation with riluzole could potentially alleviate co-occurring metabolic and amyloidogenic pathologies, in an effort to improve cognitive decline.Our early intervention study involved transgenic (APP/PS1) and knock-in (APPNL-F/NL-F) AD mice, in both male and female animals, to examine the effects of prodromal glutamatergic modulation (2-6 months) on glucose homeostasis and spatial cognition using riluzole, analyzing both on-treatment and off-treatment phases.Time since treatment and disease progression played a crucial role in the riluzole intervention's sex- and genotype-specific effects on glucose homeostasis and spatial cognition.These results highlight a profound correlation between glucose regulation, glutamatergic activity, amyloid burden, and cognitive capacity, urging further studies to explore the potential for interventions specifically targeting this interconnected system.These results, revealing a complex association between glucose, glutamatergic homeostasis, amyloid pathology, and cognitive function, advocate for further investigation into the strategic targeting of this connection to potentially improve cognitive abilities.For assessing anomia, the Boston Naming Test (BNT) serves as the most prevalent instrument. Although potentially valuable, it has been criticized for not sufficiently differentiating the fundamental cognitive processes underlying anomia.In a sample representative of various neurodegenerative dementia diseases (NDDs), the color-picture version of BNT (CP-BNT) demonstrated its validity. We also confirmed the differential capacity of CP-BNT composite indices across NDD groups.This research encompassed Alzheimer's disease (n=132), semantic variant primary progressive aphasia (svPPA, n=53), non-svPPA cases (n=33), posterior cortical atrophy (PCA, n=35), and healthy controls (n=110). Our analysis of the CP-BNT's psychometric properties focused on spontaneous naming (SN), the percentage of correct responses when semantic cues were provided, and the percentage of correct responses when word recognition cues were applied (%, % WR). To assess the discriminatory capability of the single SN metric and the combined indices (SN, percentage SC, and percentage WR), a receiver operating characteristic analysis was employed.The CP-BNT's internal consistency was found to be adequate, possessing strong convergent, divergent, and criterion validity. The varying indices within CP-BNT revealed distinct cognitive foundations. Category fluency emerged as the most potent predictor of SN, with a statistically significant correlation observed (r = 0.46, p < 0.0001). thrombin signal Auditory comprehension, as measured by sentence and word comprehension, is strongly linked to percentage of words recalled (% WR) Sentence comprehension exhibited a significant association with % WR (p=0.0001; coefficient = 0.22), and similarly, word comprehension demonstrated a significant association with % WR (p=0.0001; coefficient = 0.20). A lower visuospatial score, however, is significantly associated with a lower percentage of correct recall (% SC) (p=0.0001; coefficient = -0.02).