Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice.
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ABSTRACT:
SUBMITTER: Takeuchi H
PROVIDER: S-EPMC7096417 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer's disease. Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer's disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer's disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer's Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer's disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein ε4 (APOE ε4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer's disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer's disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer's disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer's disease.
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Project description:BackgroundStructural network alterations in Alzheimer's disease (AD) are related to worse cognitive impairment. The aim of this study was to quantify the alterations in gray matter associated with impaired cognition and their pathological biomarkers in AD-spectrum patients.MethodsWe extracted gray matter networks from 3D-T1 magnetic resonance imaging scans, and a graph theory analysis was used to explore alterations in the network metrics in 34 healthy controls, 70 mild cognitive impairment (MCI) patients, and 40 AD patients. Spearman correlation analysis was computed to investigate the relationships among network properties, neuropsychological performance, and cerebrospinal fluid pathological biomarkers (i.e., Aβ, t-tau, and p-tau) in these subjects.ResultsAD-spectrum individuals demonstrated higher nodal properties and edge properties associated with impaired memory function, and lower amyloid-β or higher tau levels than the controls. Furthermore, these compensations at the brain regional level in AD-spectrum patients were mainly in the medial temporal lobe; however, the compensation at the whole-brain network level gradually extended from the frontal lobe to become widely distributed throughout the cortex with the progression of AD.ConclusionThe findings provide insight into the alterations in the gray matter network related to impaired cognition and pathological biomarkers in the progression of AD. The possibility of compensation was detected in the structural networks in AD-spectrum patients; the compensatory patterns at regional and whole-brain levels were different and the clinical significance was highlighted.
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