Alzheimer's & Dementia最新文献

Introduction: While the role of apolipoprotein E (APOE) ε4 in Alzheimer's disease (AD) susceptibility has been studied extensively, much less is known about the differences in disease presentation in APOE ε4 carriers versus non-carriers.

Methods: To help elucidate these differences, we performed a broad analysis comparing the regional levels of six different neuroimaging biomarkers in the brains of APOE ε4 carriers versus non-carriers who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Results: We observed significant APOE ε4-associated heterogeneity in regional amyloid beta deposition, tau accumulation, glucose uptake, brain volume, cerebral blood flow, and white matter hyperintensities within each AD diagnostic group. We also observed important APOE ε4-associated differences in cognitively unimpaired individuals who converted to mild cognitive impairment/AD versus those who did not convert.

Discussion: This observed heterogeneity in neuroimaging biomarkers between APOE ε4 carriers versus non-carriers may have important implications regarding the prevention, diagnosis, and treatment of AD in different subpopulations.

Highlights: An extensive study was performed on the apolipoprotein E (APOE) ε4-associated heterogeneity in neuroimaging biomarkers from the Alzheimer's Disease Neuroimaging Initiative. Robust APOE ε4-associated increases in amyloid beta (Aβ) deposition throughout the brain, in every diagnostic group, were observed. APOE ε4-associated increases in tau pathology, decreases in glucose uptake, and increases in brain atrophy, which expand in regional scope and magnitude with disease progression, were observed. Significant sex- and age-related differences in APOE ε4-associated neuroimaging biomarker heterogeneity, with overall increases in pathological presentation in female APOE ε4 carriers, were observed. Regional differences in Aβ deposition, tau accumulation, glucose uptake, ventricle size, and white matter hyperintensities were observed in cognitively normal participants who converted to mild cognitive impairment/Alzheimer's disease, which may hold potential predictive value.

Background: This study examines whether phosphorylated plasma Tau217 ratio (pTau217R) can predict tau accumulation in different brain regions, as measured by positron emission tomography (PET) standardized uptake value ratio (SUVR), for staging Alzheimer's disease (AD).

Methods: Plasma pTau217R was measured using immunoprecipitation-mass spectrometry. Models for predicting tau PET SUVR, developed with 144 early AD individuals using [¹⁸F]MK6240, were validated in two validation sets, VS1 (98 early AD) and VS2 (47 preclinical/early AD with a different tracer, flortaucipir (Tauvid)), all amyloid-beta positive (Aβ+).

Results: The pTau217R-based model predicted tau levels up to an SUVR of 2 in multiple brain regions, effectively assessing tau status at different tau levels with receiver operating characteristic (ROC) curve areas of 0.84-0.95 in VS1 and 0.71-0.88 in VS2 (using a different tracer). It reduced PET scan needs by 65% while maintaining 95% sensitivity.

Discussion: PTau217R reliably predicts regional tau accumulation in early AD, reducing reliance on tau PET scans and broadening its clinical application.

Clinical trial registration number: NCT03887455 (ClarityAD) HIGHLIGHTS: Developed a model using plasma pTau217R to predict tau levels across brain regions. pTau217R model outperformed models based on clinical, MRI, and other blood biomarkers. The model reliably predicted tau levels exceeding tau positivity and higher thresholds. Screening with pTau217R could reduce tau PET scans by 65% at 95% sensitivity. pTau217R model aids in disease staging and monitoring in early AD.

New possibilities of biomarker-based predictive technologies for Alzheimer's disease (AD) have become more reliable as well as more accessible. Standardized clinical recommendations and guidance for counseling and disclosure in this context are not yet well developed. Our scoping review identified publications from database searches in PubMed, PsycINFO, LIVIVO, and Web of Science. Inclusion criteria were: (1) information or counseling, (2) biomarkers and a type of cognitive impairment or AD, and (3) published between 2005 and 2024. We identified 63 articles and synthesized them along the categories of staged information provision: pre-test counseling, disclosure, and post-disclosure follow-up. Most publications referred to the context of disclosure (48), followed by pre-test counseling (33), and post-disclosure follow-up (31). Some publications referred to all stages of counseling (17). Our findings highlight the need to further develop and specify comprehensive and standardized guidelines for counseling, disclosure, and post-disclosure follow-up in the context of AD biomarker testing. HIGHLIGHTS: New possibilities of biomarker-based predictive technologies for Alzheimer's disease (AD) have become more reliable and also more accessible. However, clinical recommendations and guidance for counseling and disclosure in the context of AD biomarker testing are currently not well developed. We carried out a scoping review with the aim to generate an overview of the scientific literature and guidance available regarding counseling, biomarker test result and dementia risk disclosure, and clinical management prior to and in the course of a biomarker-based diagnosis in early stages of AD. We identified 63 relevant articles. Most publications referred to the context of disclosure (48), followed by pre-test counseling (33), and post-disclosure follow-up (31). Some publications referred to all stages of counseling (17). Our findings highlight the urgent need for national and international consensus guidelines for comprehensive and staged counseling and disclosure practices. While most publications identify relevant ethical challenges posed for counseling practices in the context of AD biomarker testing, they rarely present any practical recommendations for clinicians, on how and what to counsel on a concrete level.