👤 Nikolaos Scarmeas

Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE, CR1, GMNC/CCDC50 and C16orf95/MAP1LC3B. Novel loci include BIN1 for amyloid beta and GNA12, MS4A6A, SLCO1A2 with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2. We also demonstrate that these variants have significant association with Alzheimer's disease risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of APOE, coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation. Show less

While early-life adverse experiences have been linked to late-life cognitive decline, few studies have explored war exposure. Paradoxically, one study even indicated a late-life cognitive advantage of early-childhood war exposure. In the present study, we explored these associations. We examined older adults exposed to World War II (1940-1944; Higher cognitive performance in language tasks predicted middle childhood, relative to early childhood, WWII-exposure group membership ( The present findings suggest that better cognitive performance and lower likelihood of MCI or dementia were associated with being exposed to significant hardships, such as war, during middle childhood, regardless of potentially confounding factors. Further studies are needed to shed light on this relationship. Show less