Biological subtypes of Alzheimer’s disease: a systematic review and meta-analysis

Objective: We conducted a systematic review and meta-analysis on subtype studies of Alzheimer’s disease (AD) based on postmortem and neuroimaging data, with the ultimate goal of advancing our understanding of mechanisms driving heterogeneity in AD.

Methods: EMBASE, PubMed and Web of Science databases were consulted until July 2019.

Results: Neuropathology and neuroimaging studies have consistently identified three subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex, and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex ...