Premium
P4‐091: Follow‐up of the first American report of familial Alzheimer's disease
Author(s) -
Ghetti Bernardino,
Murrell Jill,
Koeppe Robert,
Gilman Sid,
Fink John,
Miravalle Leticia,
Albin Roger,
Vidal Ruben,
Foster Norman
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1793
Subject(s) - pathology , senile plaques , white matter , cerebellar cortex , cerebellum , cerebral cortex , psychology , dementia , alzheimer's disease , neuroscience , medicine , disease , magnetic resonance imaging , radiology
Background: Familial Alzheimer’s disease associated with PSEN1 mutations has a wide spectrum of clinical presentations. Cognitive deficits are the dominant features; however, other signs and symptoms can be seen including some associated with movement disorders. Methods: Affected individuals from a family were studied clinically (2), genetically (3), and neuropathologically (1). Results: The proband, a female, reportedly began to have seizures, headaches and psychiatric problems at age 14. She attempted suicide and was considered to have conversion disorder at age 15. Her seizure disorder was treated with phenytoin and carbamazepine at age 19. Also, she was diagnosed by a psychiatrist as having adolescent adjustment reaction and reactive depression. Her family noted episodes of confusion and memory difficulty at age 27. Her memory worsened, speech became dysarthric and spasticity developed in the lower extremities at age 29. A diagnosis of spinocerebellar degeneration was considered at that time. Her condition progressed until she died at age 36. The proband’s mother was reported to have had ataxia and spasticity at age 18, dementia by 30 and died at 55. The proband’s sister developed a gait disorder at age 21, dementia at 25 and died at 47 after having been in a vegetative state for 9 years. The proband’s brother was known to have a gait disorder at age 28, but was lost to follow-up. Genetic analysis of the proband and two siblings identified a single nucleotide substitution (C for T) in exon 6 in the PSEN1 gene leading to a proline for leucine substitution at codon 166 (L166P). Autopsy of the proband showed corticospinal tract degeneration with atrophy of the cerebral hemispheres, pons, cerebellum, and rostral spinal cord. Histopathology revealed advanced stage neurofibrillary tangle and neuritic plaque pathology accompanied by prominent amyloid-b (Ab) deposition as well as “cotton wool” plaques and severe amyloid angiopathy. Conclusions: This mutation in PSEN1 results in one of the earliest onsets of symptoms and most “malignant” clinical courses reported to date. This report underscores the importance of close clinical, genetic, and neuropathologic studies to diagnose atypical presentations of a neurodegenerative disease.