rs638405

This case-control study examined genetic variation in APP processing pathway genes and their association with cerebrospinal fluid amyloid-beta 42 levels in Parkinson's disease patients (n=85) versus healthy controls (n=161). Two SNPs showed significant correlation with CSF Aβ42 in PD: APP rs466448 (lower levels, p=0.014) and APH1B rs2068143 (higher levels, p=0.002), while three SNPs correlated in controls: APP rs214484 and rs2040273, and PSEN1 rs362344 (all lower levels). Results suggest APP and APH1B genetic variants may modulate CSF Aβ42 levels in PD patients.

A case-control study of 429 Han Chinese Alzheimer's disease patients and 346 controls identified two BACE1 promoter polymorphisms (rs4938369 and rs3017608). The -918G allele (rs4938369) was significantly associated with sporadic AD risk (OR=1.667, P=0.019), with GG carriers having a 1.67-fold higher risk. The -918G/-2014T haplotype was also identified as a risk factor (P=0.016). Functional assays demonstrated that the -918G allele and the risk haplotype showed increased BACE1 transcriptional activity, particularly under hypoxia.