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P3‐088: Longitudinal study of amyloid deposition in carriers of presenilin‐1, presenilin‐2 and APP mutations
Author(s) -
Klunk William E.,
Snitz Beth E.,
Cohen Ann D.,
Price Julie C.,
Mathis Chester A.,
Aizenstein Howard J.,
Saxton Judith A.,
DeKosky Steven T.
Publication year - 2009
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.2009.04.1164
Subject(s) - presenilin , atrophy , pittsburgh compound b , amyloid precursor protein , medicine , amyloid (mycology) , gastroenterology , pathology , nuclear medicine , alzheimer's disease , disease
Background: Amyloid imaging with PiB PET allows longitudinal studies that can assess natural history in individual subjects. Subjects with mutations that cause early-onset familial AD (eFAD) are ideal for these studies, since individuals can be identified in the pre-symptomatic period and followed over time. Our objective was to follow the natural history of amyloid deposition in pre-symptomatic and symptomatic carriers of autosomal dominant mutations in presenilin-1 (PS1), PS2 and APP. Methods: Thirteen mutation carriers (28-56 years) received follow-up PiB studies over 12-24 months (nine with PS1 mutations, three with APP and one with a PS2 mutation). Clinical diagnosis varied from normal to AD. All subjects underwent PiB PET scanning and tissue ratios to cerebellum (SUVR) were calculated from 4060 min post-injection and were corrected for atrophy using co-registered MRIs. Regional delta-SUVR values between scans were calculated and compared to changes measured in 22 other subjects who had test-retest studies performed within 28 days. Results: Eleven subjects had high striatal PiB retention at baseline; two young (28 & 36 y/o) APP-V717I carriers showed no specific PiB retention in any brain region. Of the 11 subjects with striatal retention, only four showed neocortical patterns of PiB retention similar to that in late-onset AD (56 y/o APP-V717I, 55 y/o PS2-N141I and 31 & 44 y/o PS1M233L). Five subjects showed significant increases in PiB retention over 1224 months (3-of-3 APP, 1-of-1 PS2 and the 31 y/o PS1-M233L). Four of these five showed increases in PiB retention in many brain areas, but the 36 y/o PS1-V717I carrier showed an increase only in the striatum. None of the six PS1-A426P carriers or the PS1-C410Y mutation carrier (all with striatal-predominant deposition) showed an increase in any brain region despite a wide range of age (37-51) and clinical status (normal cognition to AD). Subjects with the highest striatal PiB retention showed a decrease over time. Conclusions: It is possible to track the natural history of amyloid deposition in living subjects longitudinally. In eFAD, the course of amyloid deposition is dependent on the specific mutation, and it is not clear whether all mutations will result in a pattern of amyloid deposition similar to late-onset AD.