Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation.
Six young related pre-symptomatic carriers of a His163Tyr mutation in the presenilin 1 gene who will develop early onset familial Alzheimer's disease (eoFAD), and a control group of 23 non-carriers underwent (18)F-fluorodeoxyglucose positron emission tomography (FDG PET). The mutation carriers were followed-up after 2 years. Multivariate analysis showed clear separation of carriers from non-carriers on both occasions, with the right thalamus being the region contributing most to group differentiation. Statistical parametric mapping (SPM) revealed in the carriers non-significantly lower thalamic cerebral glucose metabolism (CMRglc) at baseline and significantly decreased CMRglc in the right thalamus at follow-up. One mutation carrier was followed-up with FDG PET 10 years after baseline and showed reductions in cognition and CMRglc in the posterior cingulate and the frontal cortex. This subject was diagnosed with AD 1 year later and assessed with an additional FDG as well as an (11)C-PIB PET scan 12 years after baseline. Global cortical CMRglc and cognition were distinctly decreased. PIB binding was comparable with sporadic AD patterns but showing slightly higher striatal levels.
Schöll
Michael
M
Division of Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Almkvist
Ove
O
Axelman
Karin
K
Stefanova
Elka
E
Wall
Anders
A
Westman
Eric
E
Långström
Bengt
B
Lannfelt
Lars
L
Graff
Caroline
C
Nordberg
Agneta
A
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D000814:Aniline Compounds; D052160:Benzothiazoles; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D001786:Blood Glucose; D002250:Carbon Radioisotopes; C508853:PSEN1 protein, human; D053764:Presenilin-1; D013844:Thiazoles