RT Journal Article
SR Electronic
T1 Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer’s disease
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 1050
OP 1055
DO 10.1136/jnnp.2006.113803
VO 78
IS 10
A1 Kiri L Brickell
A1 James B Leverenz
A1 Ellen J Steinbart
A1 Malia Rumbaugh
A1 Gerard D Schellenberg
A1 David Nochlin
A1 Thomas H Lampe
A1 Ida E Holm
A1 Vivianna Van Deerlin
A1 Wuxing Yuan
A1 Thomas D Bird
YR 2007
UL http://jnnp.bmj.com/content/78/10/1050.abstract
AB Aim: Neuropathological examination of both individuals in a monozygotic (MZ) twin pair with Alzheimer’s disease (AD) is rare, especially in the molecular genetic era. We had the opportunity to assess the concordance and discordance of clinical presentation and neuropathology in three MZ twin pairs with AD.Methods: The MZ twins were identified and characterised by the University of Washington Alzheimer’s Disease Research Center. We reviewed the available clinical and neuropathological records for all six cases looking specifically for concordance and discordance of clinical phenotype, neuritic amyloid plaques (NP), neurofibrillary tangles (NFT) and Lewy related pathology (LRP).Results: Discordance in age of onset for developing AD in the MZ twins varied from 4 to 18 years. Clinical presentations also differed between twins. One twin presented with a dementia with Lewy Body clinical syndrome while the other presented with typical clinical AD. Neuropathology within the MZ twin pairs was concordant for NP and NFT, regardless of duration of disease, and was discordant for LRP. This difference was most marked in the late onset AD twin pair. One pair was found to have a mutation in presenilin-1 (PS1) (A79V) with remarkably late onset in a family member.Conclusions: MZ twins with AD can vary considerably in age of onset, presentation and disease duration. The concordance of NP and NFT pathological change and the discordance of LRP support the concept that, in AD, the former are primarily under genetic control whereas the latter (LRP) is more influenced by disease duration and environmental factors. The A79V mutation in PS1 can be associated with very late onset of dementia.