Jack, Clifford R.

AbstractIntroductionComparison of tau (flortaucipir) positron emission tomography (FTP‐PET) to autopsy is important to demonstrate the relationship of FTP‐PET to neuropathologic findings.MethodsAutopsies were performed on 26 participants who had antemortem FTP‐PET. FTP‐PET standardized uptake value ratios (SUVRs) were compared to autopsy diagnoses and Braak tangle stage. Quantitative tau burden was compared to regional FTP‐PET signal.ResultsParticipants with Braak stages of IV or greater had elevated FTP‐PET signal. FTP‐PET was elevated in participants with Alzheimer's disease. An FTP‐PET SUVR cut point of 1.29 was determined to be optimal. Quantitative measurements of hippocampal and temporal lobe tau burden were highly correlated to FTP‐PET signal (rho's from 0.61 to 0.70, P ≤ .02).DiscussionElevated FTP‐PET reflects Braak IV or greater neuropathology. Participants with primary age‐related tauopathy and hippocampal sclerosis did not show elevated FTP‐PET signal. Secondary neuropathologic diagnoses of Alzheimer's disease neuropathologic change can lead to borderline elevated FTP‐PET signal.

Abstract Introduction Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total‐tau [T‐tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging–Alzheimer's Association Research Framework. Methods We examined, in a community‐based population (N = 777, aged 50–95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T‐tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in‐house enzyme‐linked immunosorbent assays. Results Multiple variables were differentially associated with CSF NfL and T‐tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T‐tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status. Discussion Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.

AbstractIntroductionPractical algorithms predicting the probability of amyloid pathology among patients with subjective cognitive decline or mild cognitive impairment may help clinical decisions regarding confirmatory biomarker testing for Alzheimer's disease.MethodsAlgorithm feature selection was conducted with Alzheimer's Disease Neuroimaging Initiative and Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing data. Probability algorithms were developed in Alzheimer's Disease Neuroimaging Initiative using nested cross‐validation accompanied by stratified subsampling to obtain 1000 internally validated decision trees. Semi‐independent validation was conducted using Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Independent external validation was conducted in the population‐based Mayo Clinic Study of Aging.ResultsTwo algorithms were developed using age and normalized immediate recall z‐scores, with or without apolipoprotein E ε4 carrier status. Both algorithms had robust performance across data sets and when substituting different recall memory tests.DiscussionThe statistical framework resulted in robust probability estimation. Application of these algorithms may assist in clinical decision‐making for further testing to diagnose amyloid pathology.