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Basic Science and Pathogenesis.

Mari J Tokita1, Justin Y Kwan2, Andrew J Oler3

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|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Genetic risk factors APOE, TMEM106B, and MAPT showed similar prevalence in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. These findings suggest these specific genetic markers may not be uniquely associated with ALS risk.

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Area of Science:

  • Neurogenetics
  • Neurodegenerative Diseases
  • Amyotrophic Lateral Sclerosis (ALS)

Background:

  • Established neurodegenerative disease risk factors include Apolipoprotein E (APOE) and TMEM106B genotypes, and MAPT haplotypes.
  • Conflicting evidence exists regarding the association of these factors with amyotrophic lateral sclerosis (ALS).

Purpose of the Study:

  • To systematically analyze APOE, TMEM106B, and MAPT in an ALS cohort.
  • To compare their prevalence and association with disease outcomes against a broader neurodegenerative cohort.

Main Methods:

  • Analysis of participants from the NIH Neurodegenerative Disorders Clinic.
  • Whole genome sequencing and genotyping for specific SNPs (rs8070723, rs429358, rs7412, rs1990622) to determine APOE, TMEM106B, and MAPT statuses.

Main Results:

  • Preliminary analysis included 34 participants (21% ALS, 79% non-ALS).
  • APOE e4, TMEM106B risk allele, and MAPT H1 haplotype frequencies were similar between ALS and non-ALS groups.
  • No statistically significant differences were observed, likely due to small sample size.

Conclusions:

  • Observed patterns align with known risk locus associations, despite non-significant findings.
  • APOE e4 genetic risk was not enriched in the ALS cohort.
  • TMEM106B and MAPT H1 haplotype status were similar in both ALS and non-ALS cohorts, with future studies aiming to increase sample size.