Butyrylcholinesterase K and apolipoprotein ε4 affect cortical thickness and neuropsychiatric symptoms in Alzheimer's disease.
Two major genotypes are known to affect the development and progression of Alzheimer's disease (AD) and its response to cholinesterase inhibitors: the apolipoprotein E (ApoE) and butyrylcholinesterase genes (BChE). This study analyzed the effects of the BChE and ApoE genotypes on the cortical thickness of patients with AD and examined how these genotypes affect the neuropsychiatric symptoms of AD. AD-drug-naïve patients who met the probable AD criteria proposed by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association were recruited. Of 96 patients with AD, 65 were eligible for cortical thickness analysis. 3D T1-weighted images were acquired, and the cortical regions were segmented using the constrained Laplacian-based automated segmentation with proximities (CLASP) algorithm. Neuropsychiatric symptoms were measured by Neuropsychiatric Inventory (NPI) scores. BChE wild-type carriers (BChE-W) showed more thinning in the left dorsolateral prefrontal cortex, including the lateral premotor regions and anterior cingulate cortex, than did BChE-K variant carriers (BChE-K). ApoE-ε4 carriers had a thinner left medial prefrontal cortex, left superior frontal cortex, and left posterior cingulate cortex than did ApoE-ε4 non-carriers. Statistical analyses revealed that BChE-K carriers showed significantly less severe aberrant motor behavioral symptoms and that ε4 non-carriers showed less severe anxiety and indifference symptoms. The current findings show that, similar to ApoE-ε4 non-carriers, BChE-K carriers are protected from the pathological detriments of AD that affect frontal cortical thickness and neuropsychiatric symptoms. This study visually demonstrated the effects of the BChE-K and ApoE genotypes on the structural degeneration and complex aspects of the symptoms of AD.
Hye B
HB
Yoo
Hae W
HW
Lee
Sue
S
Shin
Sun-Won
SW
Park
Jung S
JS
Choi
Hee Y
HY
Jung
Jungho
J
Cha
Jong-Min
JM
Lee
Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine & SMG-SNU Boramae Medical Center, 425 Shindaebang 2-Dong, Dongjak- Gu, Seoul 156-707, Republic of Korea. benji@snu.ac.kr.
Jun-Young
JY
Lee
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002091:Butyrylcholinesterase / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D009483:Neuropsychological Tests
D053327:Apolipoprotein E4; D002091:Butyrylcholinesterase