Although brain deposition of β-amyloid (Aβ) is considered as the primum movens of Alzheimer’s disease (AD) pathology, there is a need to identify markers that may indicate which Aβ+ individuals will also display tau deposition within imminent years. In a recent study, Josephs et al. (1) searched the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for Aβ-positive individuals who remained tau-negative for at least 5 years (amyloid with low tau [ALT] group), in order to identify distinctive features between these individuals and those who develop high tau PET signal within this period. 45 Aβ-positive individuals met criteria for ALT and were compared with 157 meeting criteria for biomarker AD. ALT subjects had a lower proportion of APOE ε4 alleles, lower Aβ burden, larger hippocampal volumes, and more preserved cognition, and were less likely to develop dementia, than the biomarker AD group. A threshold of amyloid burden (i.e., Centiloid value of 50) could discriminate biomarker AD and ALT with 80% sensitivity and specificity. The results of this study support the notion that baseline characteristics of Aβ-positive individuals can help identify ALT individuals who are less likely to develop overt dementia. The authors stress the importance of adopting conservative Aβ cutpoints to be used for clinical trials, in order to better capture individuals with high risk of developing biomarker AD (=amyloid+tau pathology).
- Baseline characteristics of Aβ-positive individuals can help identify those who will remain tau-negative for at least 5 years.
- These subjects are less likely APOE ε4 carriers, have lower Aβ burden, larger hippocampal volumes, and more preserved cognition.
- Amyloid-positive with low tau are less likely to develop dementia.
Josephs KA, Weigand SD, Whitwell JL. Characterizing Amyloid-Positive Individuals With Normal Tau PET Levels After 5 Years: An ADNI Study. Neurology. 2022 May 31;98(22):e2282-e2292. doi: 10.1212/WNL.0000000000200287. Epub 2022 Mar 21. PMID: 35314506; PMCID: PMC9162162. https://pubmed.ncbi.nlm.nih.gov/35314506/