DOI: 10.1002/alz.073923 ISSN: 1552-5260

ABCA7 Mutations Can Present as Behavioral Variant Frontotemporal Dementia Without Amyloid Pathology

Allison Snyder, Rhonna Shatz
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



ABCA7 was identified as an Alzheimer’s disease (AD) risk gene in 2011 through GWAS studies and subsequently its role in pathogenesis was confirmed via in‐vivo studies demonstrating loss of ABCA7 was sufficient to the trigger amyloid cascade. The most common presentation of ABCA7 loss of function mutations is an amnestic syndrome, however it less commonly can present with behavioral or motor symptoms. While the described clinical presentation can vary, almost all cases have been associated with AD pathology. Here we present three cases of bvFTD clinical syndromes in ABCA7 mutations carriers without evidence of AD pathology.


Patients underwent a comprehensive clinical assessment including neurological history, examination, neuropsychological testing, MR brain imaging, and lumbar puncture. AD biomarkers were assessed through CSF testing. Genetic testing was obtained through CLIA certified whole genome sequencing.


We identified three individuals with mutations in ABCA7. Two of these individuals harbor the p.I1878M mutation and one with the p.W1214* mutation on genetic testing. They presented with behavioral variant frontotemporal dementia with no evidence of amyloid pathology on CSF biomarker testing.


We present three cases of symptomatic ABCA7 mutation carriers without evidence of underlying AD pathology. The exact function of ABCA7 is unknown, however its purported involvement in lipid transport and immune responses are common pathways in neurodegenerative disease and raises the possibility of converging disease cascades.

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