title: Time course of glucose metabolism in relation to cognitive performance and postmortem neuropathology in Met146Val PSEN1 mutation carriers.
abstract: Studies in carriers of mutations that cause early-onset familial Alzheimer’s disease (eoFAD) are of significant interest.We showed previously that regional glucose hypometabolism could be detected many years before disease onset in presenilin 1(PSEN1) mutation carriers. Here we studied four members of a family with a Met146Val PSEN1 mutation, two symptomatic carriers and two non-carriers, longitudinally with 18F-FDG PET over a period of about two and four years, respectively. The two mutation carriers showed global cortical glucose hypometabolism over time with the most distinct decline occurring in the posterior cingulate, the parietal and parietotemporal cortex, which was also observed when compared with a group of 23 healthy controls and a group of 27 sporadic Alzheimer’s disease (sAD) patients. This decline correlated with cognitive deterioration overtime as measured by neuropsychological tests. Postmortem examination of brain tissue revealed substantially elevated levels of AD type neuropathology in terms of neuritic plaques and neurofibrillary tangles in the two mutation carriers compared with a reference group of 249 sAD patients. In the mutation carriers, the amount of neuritic plaques but not neurofibrillary tangles correlated hereby significantly with regional glucose metabolism as measured by 18F-FDG on the last scanning occasions, which were performed four and approximately five years before death, respectively. We here show that FDG PET can depict in vivo the aggressive disease progression in eoFAD mutation carriers in relationship to neuropathology.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Division of Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Schöll
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.forename: Matti
authors.initials: M
authors.lastname: Viitanen
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011180:Postmortem Changes; D053764:Presenilin-1 / Q000235:genetics*; D013223:Statistics as Topic; D013997:Time Factors; D014633:Valine / Q000235:genetics
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1; D019788:Fluorodeoxyglucose F18; D008715:Methionine; D014633:Valine; D005947:Glucose