<![CDATA[Background: Alzheimer’s disease (AD) is the leading cause of dementia in older adults, yet early biological confirmation remains challenging in primary care. The plasma amyloid-β42/β40 ratio has emerged as a minimally invasive marker of cerebral amyloid burden. Objective: This study evaluated the diagnostic potential of the plasma amyloid-β42/β40 ratio for early AD detection in elderly primary-care patients and examined its relationship with cognitive performance. Methods: A case-control study was conducted among 20 elderly participants (≥65 years) from community health centres (Puskesmas) in Semarang, Indonesia, including 10 patients with clinically diagnosed AD and 10 age- and sex-matched cognitively healthy controls. Plasma amyloid-β42 and amyloid-β40 were measured using ELISA. Cognitive function was assessed using the MMSE and MoCA. Statistical analyses included independent t-tests, Pearson correlation, ROC analysis, and Firth bias-reduced logistic regression. Results: The plasma amyloid-β42/β40 ratio was significantly lower in the AD group than in controls (0.115 ± 0.005 vs 0.138 ± 0.004; p<0.001), as was amyloid-β42 concentration (35.3 ± 3.1 vs 43.3 ± 2.6 pg/mL; p<0.001). The ratio showed strong correlations with MMSE (r=0.984, p<0.001) and MoCA (r=0.988, p<0.001) scores. ROC analysis demonstrated complete group separation (AUC=1.000) at a cut-off ≤0.126, with 100% sensitivity and specificity. Each 0.01-unit decrease in the ratio was associated with increased AD odds (Firth-adjusted OR=25.79; 95% CI 1.79–372.64; p=0.017). Conclusion: The plasma amyloid-β42/β40 ratio showed strong discrimination between AD and healthy ageing and closely reflected cognitive impairment. However, the small sample size and complete separation require validation in larger, diverse cohorts before clinical implementation.]]>
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