Abstract
INTRODUCTION
The ɛ4 allele of the apolipoprotein E gene (APOE ɛ4) is the strongest genetic risk factor for Alzheimer’s disease (AD), but the mechanisms connecting APOE ɛ4 to AD are not clear.
METHODS
Participants (n = 596) were from two clinical-pathological studies. Tissues from dorsolateral prefrontal cortex were examined to identify 8425 proteins. Post mortem pathological assessment used immunohistochemistry to obtain amyloid beta (Aβ) load and tau tangle density.
RESULTS
In separate models, APOE ɛ4 was associated with 18 proteins, which were associated with Aβ and tau tangles. Examining the proteins in a single model identified Netrin-1 and secreted frizzled-related protein 1 (SFRP1) as the two proteins linking APOE ɛ4 with Aβ with the largest effect sizes and Netrin-1 and testican-3 linking APOE ɛ4 with tau tangles.
DISCUSSION
We identified Netrin-1, SFRP1, and testican-3 as the most promising proteins that link APOE ɛ4 with Aβ and tau tangles.
Highlights
Of 8425 proteins extracted from prefrontal cortex, 18 were related to APOE ɛ4.
The 18 proteins were also related to amyloid beta (Aβ) and tau.
The 18 proteins were more related to APOE ɛ4 than other AD genetic risk variants.
Netrin-1 and secreted frizzled-related protein 1 were the two most promising proteins linking APOE ɛ4 with Aβ.
Netrin-1 and testican-3 were two most promising proteins linking APOE ɛ4 with tau.
If you do not see content above, kindly GO TO SOURCE.
Not all publishers encode content in a way that enables republishing at Neuro.vip.
This post is Copyright: Shahram Oveisgharan,
Lei Yu,
Katia de Paiva Lopes,
Shinya Tasaki,
Yanling Wang,
Vilas Menon,
Julie A. Schneider,
Nicholas T. Seyfried,
David A. Bennett | June 10, 2024