ABSTRACT
OBJECTIVE: To examine the influence of the APOE genotype on levels of beta-amyloid (Abeta) plaque load and atrophy in patients with Alzheimer disease (AD) in vivo. METHODS: Thirty-two patients with moderate AD were divided into carriers and noncarriers of the epsilon4 allele. These groups were matched for age, disease duration, education, and cognitive impairment. In all subjects, [11C]PIB-PET was performed for measurement of cerebral Abeta plaque deposition and cranial MRI for the assessment of gray matter volume by voxel-based morphometry (VBM) and for correction of partial volume effects (PVE) in the PET data. Voxel-based comparisons (SPM5) were performed between patient groups and healthy control populations and completed with multiple regression analyses between imaging data and epsilon4 allele frequency. RESULTS: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both epsilon4-positive and epsilon4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in epsilon4-positive patients in bilateral temporoparietal and frontal cortex, surviving PVE correction. VBM analysis demonstrated comparable levels of atrophy in both patient groups. Regression analyses revealed a linear association between higher epsilon4 allele frequency and stronger temporoparietal Abeta plaque deposition, independently of other confounds. No major correlation between epsilon4 allele frequency and gray matter decrease was observed. CONCLUSION: These results indicate that the epsilon4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Abeta plaque deposition in epsilon4-positive patients with AD compared to age-matched epsilon4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Abeta plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apolipoproteins E/genetics , Brain/pathology , Plaque, Amyloid/pathology , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/metabolism , Aniline Compounds , Apolipoprotein E4/genetics , Benzothiazoles , Brain/diagnostic imaging , Brain/metabolism , Carbon Radioisotopes , DNA Mutational Analysis , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing , Genotype , Humans , Male , Middle Aged , Plaque, Amyloid/metabolism , Positron-Emission Tomography , Risk Factors , ThiazolesABSTRACT
Epidemiological studies identified a higher risk of developing Alzheimer's disease (AD) among subjects with elevated cholesterol levels. This association may be caused by a modulation of the amyloid precursor protein (APP) processing in response to the cellular cholesterol content. High cholesterol levels may favor the amyloidogenic pathway by inhibition of the alpha-secretase probably leading to elevated beta-Amyloid (Abeta) production. The identification of a linkage peak on chromosome 10q using high Abeta as quantitative trait led us to examine polymorphisms of genes located on chromosome 10 involved in cholesterol metabolism, like Lipase A (LIPA), Cholesterol 25 hydroxylase (CH25H), and FLJ22476, a high density lipoprotein binding related protein. Using 286 patients with AD and 162 controls we analyzed several single nucleotide polymorphisms (SNPs) within LIPA, CH25H, and FLJ22476. None of the polymorphisms showed significant association with AD which contradicts recent findings on CH25H. From our results we conclude that the investigated genetic variations do not contribute to the genetic risk of AD.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Cholesterol/genetics , Cholesterol/metabolism , Chromosomes, Human, Pair 10/genetics , Linkage Disequilibrium/genetics , Aged , Alzheimer Disease/epidemiology , Chromosome Mapping/methods , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Germany/epidemiology , Humans , Male , Risk Assessment/methods , Risk Factors , Statistics as TopicSubject(s)
Cognition Disorders/complications , Dementia/complications , Depressive Disorder/complications , Dementia/diagnosis , Dementia/psychology , Depressive Disorder/diagnosis , Depressive Disorder/etiology , Diagnosis, Differential , Female , Humans , Male , Neurocognitive Disorders/complications , Neurocognitive Disorders/diagnosisABSTRACT
The case of a 33-year-old woman with a right hemisphere lesion after subarachnoid bleed is reported. She developed the false belief that her husband, her mother, her children, and herself had been replaced by doubles after the birth of her fourth daughter. The multifactorial etiology of the Capgras delusion is discussed with a brief review of the literature.
Subject(s)
Capgras Syndrome/psychology , Delusions/psychology , Neurocognitive Disorders/psychology , Puerperal Disorders/psychology , Adult , Family , Female , Follow-Up Studies , Humans , Life Change Events , Personality Development , Psychoanalytic Theory , Subarachnoid Hemorrhage/complicationsABSTRACT
Primary degenerative dementia of the Alzheimer type and multiinfarct dementia exhibit differences in cerebrovascular blood flow velocity profiles, which were investigated by transcranial Doppler sonography. The pulsatility indices, as angle-independent parameters of peripheral vascular resistence, measured in middle cerebral and basilar arteries of patients with multiinfarct dementia were significantly increased (p less than 0.005) compared with cases of primary degenerative dementia of the Alzheimer type and with healthy age-matched controls.
