Apolipoprotein E Alleles Across the Spectrum of Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis

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We conducted a systematic review and meta-analysis of associations between apolipoprotein E (APOE) alleles and frontotemporal lobar degeneration (FTLD)-spectrum disorders. MEDLINE, Embase, CENTRAL, and Google Scholar were searched. APOE2 and APOE4 carrier status were compared between FTLD-spectrum disorders and healthy controls (HCs) or individuals with Alzheimer’s disease (AD). Forty studies were included. APOE4 carriage was more frequent in frontotemporal dementia (FTD) compared with HC (OR = 1.72; 95% CI = 1.45–2.04) and less common than in AD (OR = 0.35; 95% CI = 0.29–0.42). In contrast, APOE2 carriage was less prevalent in FTD relative to HC (OR = 0.83; 95% CI = 0.70–0.98) but more frequent compared with AD (OR = 1.80; 95% CI = 1.29–2.52). APOE4 effects were most pronounced in behavioral variant FTD. In clinically confirmed progressive supranuclear palsy (PSP), APOE4 carriage was not associated with PSP. Analysis restricted to pathologically confirmed PSP cases, however, showed lower APOE4 carriage in PSP than in healthy controls (OR = 0.78, 95% CI = 0.65–0.94), although this association failed to reach the multiplicity-adjusted significance threshold. APOE2 carriage was not associated with PSP in either clinically established or pathologically confirmed samples. Evidence was insufficient to establish or exclude associations for other FTLD-spectrum disorders because of the limited available data. In conclusion, APOE alleles show distinct associations across the FTLD spectrum.

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