Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia.

Hippocampal subfield associations with memory depend on stimulus modality and retrieval mode.

Hippocampal atrophy is a well-known feature of age-related memory decline, and hippocampal subfields may contribute differently to this decline. In this cross-sectional study, we investigated the associations between hippocampal subfield volumes and performance in free recall and recognition memory tasks in both verbal and visual modalities in older adults without dementia. We collected MRIs from 97 (41 males) right-handed participants aged over 60.

Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease.

Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.

Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.

APOEε4 potentiates amyloid β effects on longitudinal tau pathology.

The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences the pathophysiological progression of Alzheimer's disease (AD) are poorly understood. Here we tested the association of APOEε4 carriership and amyloid-β (Aβ) burden with longitudinal tau pathology. We longitudinally assessed 94 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([F]AZD4694) and tau ([F]MK-6240) at baseline, as well as a 2-year follow-up tau-PET scan.

Verbal memory formation across PET-based Braak stages of tau accumulation in Alzheimer's disease.

A classical early sign of typical Alzheimer's disease is memory decline, which has been linked to the aggregation of tau in the medial temporal lobe. Verbal delayed free recall and recognition tests have consistently probed useful to detect early memory decline, and there is substantial debate on how performance, particularly in recognition tests, is differentially affected through health and disease in older adults. Using PET-Braak staging, we investigated delayed recall and recognition memory dysfunction across the Alzheimer's disease spectrum.

ε4 associates with microglial activation independently of Aβ plaques and tau tangles.

Animal studies suggest that the apolipoprotein E ε4 (ε4) allele is a culprit of early microglial activation in Alzheimer's disease (AD). Here, we tested the association between ε4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomography for amyloid-β (Aβ; [F]AZD4694), tau ([F]MK6240), and microglial activation ([C]PBR28).

Medial temporal tau predicts memory decline in cognitively unimpaired elderly.

Alzheimer's disease can be detected in living people using biomarkers of amyloid-β and tau, even in the absence of cognitive impairment during the preclinical phase. [F]-MK-6420 is a high-affinity PET tracer that quantifies tau neurofibrillary tangles, but its ability to predict cognitive changes associated with early Alzheimer's disease symptoms, such as memory decline, is unclear. Here, we assess the prognostic accuracy of baseline [F]-MK-6420 tau-PET for predicting longitudinal memory decline in asymptomatic elderly individuals.

CSF tau368/total-tau ratio reflects cognitive performance and neocortical tau better compared to p-tau181 and p-tau217 in cognitively impaired individuals.

Introduction: Cerebrospinal fluid (CSF) tau biomarkers are reliable diagnostic markers for Alzheimer's disease (AD). However, their strong association with amyloid pathology may limit their reliability as specific markers of tau neurofibrillary tangles. A recent study showed evidence that a ratio of CSF C-terminally truncated tau (tau368, a tangle-enriched tau species), especially in ratio with total tau (t-tau), correlates strongly with tau PET tracer uptake.

The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of [F]MK6240 Tau PET in Target Regions.

6-(fluoro-F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([F]MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off-target retention on the longitudinal quantification of [F]MK6240 in target regions. We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzheimer disease spectrum with longitudinal [F]MK6240 SUVs and SUV ratios (SUVRs) (mean ± SD, 2.

Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer's disease.

Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ ([F]AZD4694) and tau ([F]MK-6240), as well as CSF GFAP and YKL-40 measures.

Comparing tau status determined via plasma pTau181, pTau231 and [F]MK6240 tau-PET.

Background: Tau in Alzheimer's disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [F]MK6240 tau-PET, plasma pTau181 and pTau231.

Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum.

Importance: Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CSF GFAP.

Objective: To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP.