Cerebral Glucose Metabolism in Dizygotic Twin Pairs Discordant for Alzheimer’s Disease

Abstract

Positron emission tomography (PET) with 2-deoxy-2[¹⁸F]-fluoro-D-glucose (FDG) can be used to estimate regional cerebral glucose metabolism (rCMRgluc). FDG-PET studies have shown rCMRgluc to be reduced especially in temporal and parietal cortices in Alzheimer’s disease (AD). A previous study on monozygotic twins discordant for AD showed that the rCMRgluc of the non-demented twins is reduced significantly in the lateral temporal and parietal cortices compared to unrelated controls. In this study we examined 9 pairs of dizygotic twins discordant for AD with FDG-PET. The rCMRgluc of the demented twins was 16% lower in the prefrontal cortex (p = 0.04), 20% lower in the hippocampus (p = 0.002) and 15% lower in the lateral temporal cortex (p = 0.003) compared to controls. The non-demented twins showed no such reductions on any cortical region compared to unrelated control subjects. This implies that both genes and environment, and not genes alone, are causative in the pathogenesis of AD.

Brain Glucose Hypometabolism and Oxidative Stress in Preclinical Alzheimer's Disease

“…In recent years, several FDG–PET studies have shown that brain glucose hypometabolism within key brain regions accurately distinguishes AD from normal aging, precedes cognitive decline and the onset of dementia among normal elderly and presymptomatic FAD individuals, and can be found in cognitively normal subjects with subjective memory complaints and in carriers of the APOE E4 genotype. FDG–PET studies in dizygotic twins discordant for AD are also of great interest as a new strategy to tap preclinical CMRglc abnormalities in AD and examine the influence of genetics and the environment in the onset of dementia 102,103 . FDG–PET neuroimaging is therefore considered a candidate modality for the detection of early AD brain changes prior to the onset of clinical symptoms of the disease.…”

Voxel-based analysis of cerebral glucose metabolism in mono- and dizygotic twins discordant for Alzheimer disease

“…As stated above, the results based on manual drawing of ROIs of the twins have been previously published (MZ twins20 and DZ twins21). However, this is the first FDG-PET study on twin pairs discordant for AD in which both MZ and DZ twin pairs were studied.…”

“…Attenuation was performed with two rotating rod sources (nominal activity 400 MBq each), and iterative segmented attenuation correction was used. Cerebral GMR was determined using a Gjedde–Patlak plot27 according to a protocol reported previously 21. Written informed consent was obtained from all subjects before PET imaging.…”

“…The mean injected activity was 257.4 (45.9) MBq. The PET data of the MZ20 and DZ21 twins have been previously published using manually drawn ROIs.…”

“…The finding can be an indication of early, preclinical AD pathogenesis or an increased familial risk of AD. In a similar study including nine DZ twin pairs discordant for AD, no differences were found between non-demented co-twins and controls21 based on a region of interest (ROI) analysis.…”