What does this research mean for the field?

Genetic variants in the AKAP9 and STXBP6 loci are associated with a mismatch between tau pathology and neurodegeneration, leading to higher-than-expected regional neurodegeneration given tau levels. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To identify the genetic architecture that influences individual variability and mismatch between cortical tau pathology burden and brain neurodegeneration.

September 3, 2026CNS Neuroscience & TherapeuticsOpen Access

GWAS of Tau‐Neurodegeneration Mismatch Identifies New Risk Loci for Susceptibility to Tau

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Authors

FNFardin Nabizadeh HMHanieh Mohamadi F(for the Alzheimer's Disease Neuroimaging Initiative (ADNI)

Discussion

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Overview

Genome-wide association study reveals novel risk loci linked to elevated neurodegeneration relative to tau burden in Alzheimer's cohorts, indicating genetic drivers of tau susceptibility.

Key Points

To identify the genetic architecture that influences individual variability and mismatch between cortical tau pathology burden and brain neurodegeneration.
Conducted a genome-wide association study (GWAS) measuring the residual relationship between cortical tau on PET and cortical thickness on MRI.
Analyzed genetic and neuroimaging data from N=794 participants across the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) cohorts.
Identified two novel loci surpassing the genome-wide significance threshold (p ≤ 5 × 10⁻⁸) for tau/neurodegeneration residuals on chromosomes 7 and 14.
The directly genotyped variant rs9323573 in STXBP6 on chromosome 14 reached genome-wide significance (minor allele frequency [MAF] = 0.221, p = 2.60 × 10⁻⁸).
The directly genotyped variant rs9784993 in AKAP9 on chromosome 7 reached genome-wide significance (MAF = 0.197, p = 4.92 × 10⁻⁸), with minor G alleles at both loci associating with lower residuals and higher-than-expected neurodegeneration relative to tau load.

Cite This Study

Nabizadeh et al. (2026) studied this question.

synapsesocial.com/papers/6a99355b636c6408cfa7d90d https://doi.org/10.1002/cns.71125

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September 3, 2026CNS Neuroscience & TherapeuticsOpen Access

GWAS of Tau‐Neurodegeneration Mismatch Identifies New Risk Loci for Susceptibility to Tau

View Full Paper

Ask AI

Bookmark

Authors

FNFardin Nabizadeh HMHanieh Mohamadi F(for the Alzheimer's Disease Neuroimaging Initiative (ADNI)

Discussion

Member takes

Overview

Genome-wide association study reveals novel risk loci linked to elevated neurodegeneration relative to tau burden in Alzheimer's cohorts, indicating genetic drivers of tau susceptibility.

Key Points

To identify the genetic architecture that influences individual variability and mismatch between cortical tau pathology burden and brain neurodegeneration.
Conducted a genome-wide association study (GWAS) measuring the residual relationship between cortical tau on PET and cortical thickness on MRI.
Analyzed genetic and neuroimaging data from N=794 participants across the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) cohorts.
Identified two novel loci surpassing the genome-wide significance threshold (p ≤ 5 × 10⁻⁸) for tau/neurodegeneration residuals on chromosomes 7 and 14.
The directly genotyped variant rs9323573 in STXBP6 on chromosome 14 reached genome-wide significance (minor allele frequency [MAF] = 0.221, p = 2.60 × 10⁻⁸).
The directly genotyped variant rs9784993 in AKAP9 on chromosome 7 reached genome-wide significance (MAF = 0.197, p = 4.92 × 10⁻⁸), with minor G alleles at both loci associating with lower residuals and higher-than-expected neurodegeneration relative to tau load.

Cite This Study

Nabizadeh et al. (2026) studied this question.

synapsesocial.com/papers/6a99355b636c6408cfa7d90d https://doi.org/10.1002/cns.71125

View Full Paper

Ask AI

Bookmark