PICALM rs3851179 Variants Modulate Left Postcentral Cortex Thickness, CSF Amyloid β42, and Phosphorylated Tau in the Elderly

PICALM rs3851179, one of the genes most frequently linked to susceptibility of late-onset Alzheimer's disease (LOAD), plays a crucial role in regulating amyloid precursor protein, and amyloid beta (A beta) transcytosis. To explore the effects of PICALM and AD continuum stage on cortex thickness, CSF A beta, and tau, 188 cognitively normal controls, 261 MCI patients, and 140 early LOAD patients were recruited, and each group was divided into rs3851179 A-carriers and GG-carriers. A full factorial ANCOVA was used to analyze the main effects and interactive effects of AD continuum stage, and PICALM. The interactive effects of AD continuum stage and PICALM on cortex thickness and CSF biomarkers were not significant. The main effect of PICALM was significant on the left postcentral cortex thickness, and the cortex thickness of A-carriers was less than that of GG-carriers. The rs3851179 A-carriers displayed higher A beta 42 levels and A beta 42/40 ratios, and lower P/T-tau ratios, compared with GG-carriers. A higher MMSE score was found in A-carriers among the LOAD patients. In conclusion, the main effects of PICALM were independent of AD continuum stage, and PICLAM rs3851179 genotypes may modulate left postcentral cortex thickness, A beta 42 level, and P/T-tau ratio. The rs3851179 A-allele may protect the cognitive function of LOAD patients.

Automated summary

The study found that the PICALM rs3851179 gene variant is associated with susceptibility to late-onset Alzheimer's disease (LOAD) and plays a crucial role in regulating amyloid precursor protein and amyloid beta transcytosis. The research confirms the effects of PICALM on cortex thickness, CSF amyloid beta, and tau levels and suggests that the rs3851179 variant may protect cognitive function in LOAD patients.