New insights into atypical Alzheimer's disease in the era of biomarkers

Jonathan Graff-Radford*, Keir X. X. Yong, Liana G. Apostolova, Femke H. Bouwman, Maria Carrillo, Bradford C. Dickerson, Gil D. Rabinovici, Jonathan M. Schott, David T. Jones, Melissa E. Murray

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.
Original languageEnglish
Pages (from-to)222-234
Number of pages13
JournalThe Lancet Neurology
Issue number3
Publication statusPublished - 1 Mar 2021

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