ε4 allele status modulates the spatial patterns of progressive atrophy in the temporal lobes after mild traumatic brain injury.

Introduction: We evaluated how the apolipoprotein E () ε4 allele modulated the spatial patterns of longitudinal atrophy in the Alzheimer's disease-vulnerable brain areas of patients with mild traumatic brain injury (mTBI) from the acute to chronic phase post injury.

Methods: Fifty-nine adult patients with acute mTBI and 48 healthy controls with ε4 allele testing underwent T1-weighted magnetic resonance imaging and neuropsychological assessments with 6 to 12 months of follow-up. Progressive brain volume loss was compared voxel-wise in the temporal lobes.

Results: Patients with the ε4 allele presented significant longitudinal atrophy in the left superior and middle temporal gyri, where the progressive gray matter volume loss predicted longitudinal impairment in language fluency, whereas mTBI ε4 allele noncarriers showed mainly significant longitudinal atrophy in the medial temporal lobes, without significant neuropsychological relevance.

Discussion: The atrophy progression observed in mTBI patients with the ε4 allele may increase the possibility of developing a specific phenotype of Alzheimer's disease with language dysfunction.

Highlights: The apolipoprotein E () ε4 allele and mild traumatic brain injury (mTBI) are risk factors for Alzheimer's disease (AD) progression.It is unclear how the interaction of mTBI with the ε4 allele impacts the progressive atrophy topography in AD-vulnerable brain regions.In this study, patients with the ε4 allele showed progressive atrophy patterns similar to the early stage of logopenic variant of primary progressive aphasia (lvPPA) phenotype of AD. ε4 allele carriers with mTBI history may be at the risk of developing a given AD phenotype with language dysfunction.