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

Ioannis Liampas; Antonis Polyviou; Silvia Demiri; Gerasimos Malataras; Vasilis Oikonomakis; Vasileios Siokas; Odysseas Kargiotis; Zinovia-Maria Kefalopoulou; Elisabeth Chroni; Efthimios Dardiotis

doi:10.3390/ijms27177752

PubMed · 42737648

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

Ioannis Liampas·Antonis Polyviou·Silvia Demiri·Gerasimos Malataras·Vasilis Oikonomakis·Vasileios Siokas·Odysseas Kargiotis·Zinovia-Maria Kefalopoulou·Elisabeth Chroni·Efthimios Dardiotis

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Abstract

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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Humans Frontotemporal Lobar Degeneration Alleles Apolipoprotein E4 Apolipoproteins E Alzheimer Disease Apolipoprotein E2 Frontotemporal Dementia Genetic Predisposition to Disease Supranuclear Palsy, Progressive corticobasal degeneration corticobasal syndrome frontotemporal dementia motor neuron disease progressive supranuclear palsy Journal Article Systematic Review Meta-Analysis Review

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Ioannis Liampas, Antonis Polyviou, Silvia Demiri, Gerasimos Malataras, Vasilis Oikonomakis, Vasileios Siokas, Odysseas Kargiotis, Zinovia-Maria Kefalopoulou, Elisabeth Chroni, Efthimios Dardiotis. 2026-08-29. Apolipoprotein E Alleles Across the Spectrum of Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.. https://doi.org/10.3390/ijms27177752

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