High PIB retention in Alzheimer's disease is an early event with complex relationship with CSF biomarkers and functional parameters.
BACKGROUND
New in vivo amyloid PET imaging tracers, such as (11)C-PIB, provide possibilities to deeper understand the underlying pathological processes in Alzheimer's disease (AD). In this study we investigated how (11)C-PIB retention is related to cerebral glucose metabolism, episodic memory and CSF biomarkers.


METHODS
Thirty-seven patients with mild AD and 21 patients with mild cognitive impairment (MCI) underwent PET examinations with the amyloid tracer (11)C-PIB, (18)F-FDG for measurement of regional cerebral metabolic rate of glucose (rCMRglc), assessment of episodic memory and assay of cerebral spinal fluid (CSF) levels of amyloid-beta (Abeta(1-42)), total tau and phosphorylated tau respectively. Analyses were performed using Statistical Parametric Mapping (SPM) and regions of interest (ROIs).


RESULTS
Pooled data from AD and MCI patients showed strong correlations between (11)C-PIB retention, levels of CSF biomarkers (especially Abeta(1-42)), rCMRglc and episodic memory. Analysis of the MCI group alone revealed significant correlations between (11)C-PIB retention and CSF biomarkers and between CSF biomarkers and episodic memory respectively. A strong correlation was observed in the AD group between rCMRglc and episodic memory as well as a significant correlation between (11)C-PIB retention and rCMRglc in some cortical regions. Regional differences were observed as sign for changes in temporal patterns across brain regions.


CONCLUSIONS
A complex pattern was observed between pathological and functional markers with respect to disease stage (MCI versus AD) and brain regions. Regional differences over time were evident during disease progression. (11)C-PIB PET and CSF Abeta(42) allowed detection of prodromal stages of AD. Amyloid imaging is useful for early diagnosis and evaluation of new therapeutic interventions in AD.
Forsberg
A
A
Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Almkvist
O
O
Engler
H
H
Wall
A
A
Långström
B
B
Nordberg
A
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose