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Familial language network vulnerability in primary progressive aphasia.
Sandra Weintraub1, Benjamin Rader2, Christina Coventry2
1From the Mesulam Cognitive Neurology and Alzheimer's Disease Center (S.W., B.M.R., C.C., J.S., J.W., B.B., E.J.R., M.M.M.), Department of Psychiatry and Behavioral Sciences (S.W., E.J.R.), and Department of Neurology (B.B., M.M.M.), Northwestern Feinberg School of Medicine, Chicago, IL; Department of Epidemiology (B.M.R.), Boston University School of Public Health, MA; Northwestern University Weinberg School of Arts and Sciences (K.A.G.), Evanston, IL; and Department of Psychiatry (G.C., E.M.R.), Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. sweintraub@northwestern.edu.
Familial language network vulnerability may underlie some primary progressive aphasia (PPA) cases. This vulnerability can impair language acquisition or predispose the network to neurodegeneration, explaining selective symptom presentation.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Primary progressive aphasia (PPA) is a neurodegenerative disorder affecting language.
- The etiology of PPA, particularly familial forms, remains incompletely understood.
- Investigating early cortical vulnerability offers insights into PPA pathogenesis.
Observation:
- A family with PPA and developmental language disabilities underwent comprehensive assessment.
- Neuropsychological testing revealed a developmental dyslexia pattern in affected siblings.
- Structural MRI showed reduced left hemisphere language area volume and decreased cortical connectivity in siblings.
Findings:
- Siblings exhibited a distinct pattern of cognitive deficits and neuroanatomical differences in language networks.
- Cortical connectivity was reduced between key language processing areas.
- No specific genetic mutations linked to dyslexia or dementia were identified in this cohort.
Implications:
- Findings support a model of familial language network vulnerability contributing to PPA.
- This vulnerability may manifest as early language acquisition deficits or later neurodegeneration.
- Understanding this vulnerability could explain selective network targeting in neurodegenerative diseases.
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