The impact of chronic and acute sleep deprivation on key Alzheimer's disease biomarkers: a systematic review and meta-analysis.

BACKGROUND: Sleep disruption is recognized as a risk factor for Alzheimer’s disease (AD). Both chronic and acute sleep deprivation (SD) may increase cerebrospinal fluid (CSF) levels of amyloid-beta (Aβ) and tau, potentially complicating early AD diagnoses. Some studies also suggest an inverse relationship in plasma biomarker levels, although these effects remain poorly characterized. METHODS: We conducted a systematic review and meta-analysis to examine whether SD elevates CSF concentrations of key AD biomarkers (Aβ40, Aβ42, total tau [t-tau], phosphorylated tau [p-tau]) in individuals without established AD. RESULTS: Six studies (n = 169 participants) were included. Pooled results showed that SD significantly raised CSF Aβ40 (mean difference [MD]: 31.88, 95% CI: 25.61–38.15) and Aβ42 (MD: 37.32, 95% CI: 32.67–41.97 after sensitivity analysis). While initial analyses suggested inconsistent findings for t-tau and p-tau, excluding outlier data consistently revealed elevated levels in both (t-tau MD: 37.81, 95% CI: 23.27–52.35; p-tau MD: 1.01, 95% CI: 0.26–1.77). Possible publication bias was noted, but overall findings indicate that SD may cause meaningful biomarker fluctuations. CONCLUSION: Short- or long-term SD may transiently elevate CSF Aβ and tau, underscoring the importance of assessing recent sleep history when interpreting AD biomarkers. Although not directly evaluated here, preliminary data suggest plasma biomarkers might move in the opposite direction, warranting further investigation. Clinically, these results highlight the potential impact of sleep patterns on biomarker-driven AD risk assessments. Addressing SD could thus be a valuable target for both optimizing diagnostic accuracy and potentially slowing early neurodegenerative processes.