Details

Autor(en) / Beteiligte

• Chang, Y.‐T.
• Huang, C.‐W.
• Huang, S.‐H.
• Hsu, S.‐W.
• Chang, W.‐N.
• Lee, J.‐J.
• Chang, C.‐C.

Titel

Genetic interaction is associated with lower metabolic connectivity and memory impairment in clinically mild Alzheimer's disease

Ist Teil von

• Genes, brain and behavior, 2019-06, Vol.18 (5), p.e12490-n/a

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2019

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Metabolic connectivity as showed by [18F] fluorodeoxyglucose (FDG) positron emission tomography (FDG‐PET) reflects neuronal connectivity. The aim of this study was to investigate the genetic impact on metabolic connectivity in default mode subnetworks and its clinical‐pathological relationships in patients with Alzheimer's disease (AD). We separately investigated the modulation of 2 default mode subnetworks, as identified with independent component analysis, by comparing APOE‐ε4 carriers to noncarriers with AD. We further analyzed the interaction effects of APOE (APOE‐ε4 carriers vs noncarriers) with PICALM (rs3851179‐GG vs rs3851179‐A‐allele carriers) on episodic memory (EM) deficits, reduction in cerebral metabolic rate for glucose (CMRgl) and decreased metabolic connectivity in default mode subnetworks. The metabolic connectivity in the ventral default mode network (vDMN) was positively correlated with EM scores (β =0.441, P < .001). The APOE‐ε4 carriers had significantly lower metabolic connectivity in the vDMN than the APOE‐ε4 carriers (t(96) = −2.233, P = .028). There was an effect of the APOE‐PICALM (rs3851179) interactions on reduced CMRgl in regions of vDMN (P < .001), and on memory deficits (F3,93 =5.568, P = .020). This study identified that PICALM may modulates memory deficits, reduced CMRgl and decreased metabolic connectivity in the vDMN in APOE‐ε4 carriers. [18F] FDG‐PET‐based metabolic connectivity may serve a useful tool to elucidate the neural networks underlying clinical‐pathological relationships in AD. Metabolic connectivity in ventral default mode network (vDMN) was related to episodic memory performance in patients with mild Alzheimer's disease. APOE‐ε4 carrier genotype has a detrimental effect on metabolic connectivity in the vDMN.