TY - JOUR

T1 - Cerebral serotonin 4 receptors and amyloid-β in early Alzheimer's disease

AU - Madsen, Karine

AU - Neumann, Wolf-Julian

AU - Holst, Klaus Kähler

AU - Marner, Lisbeth

AU - Haahr, Mette Thorlund

AU - Lehel, S

AU - Knudsen, Gitte Moos

AU - Hasselbalch, Steen

PY - 2011

Y1 - 2011

N2 - The 5-HT4 receptor may play a role in memory and learning and 5-HT4 receptor activation has been suggested to modulate acetylcholine release and to reduce amyloid-ß (Aß) accumulation. The aim of this study was for the first time to investigate the in vivo cerebral 5-HT4 receptor binding in early Alzheimer disease (AD) patients in relation to cortical Aß burden. Eleven newly diagnosed untreated AD patients (mean MMSE 24, range 19–27) and twelve age- and gender-matched healthy controls underwent a two-hour dynamic [11C]SB207145 PET scan to measure the binding potential of the 5-HT4 receptor. All AD patients and eight healthy controls additionally underwent a [11C]PIB PET scan to measure the cortical Aß burden. When AD patients were defined on clinical criteria, no difference in cerebral 5-HT4 receptor binding between AD patients and healthy controls was found (p = 0.54). However, when individuals were reassigned to groups according to their amyloid status, the PIB-positive individuals had 13% higher 5-HT4 receptor levels than PIB-negative individuals (p = 0.02) and the importance of classification of groups is emphasized. The 5-HT4 receptor binding was a positively correlated to Aß burden (p = 0.03) and negatively to MMSE score of the AD patients (p = 0.02). Our data suggests that cerebral 5-HT4 receptor upregulation starts at a preclinical stage of and continues while dementia is still at a mild stage, which contrasts other receptor subtypes. We speculate that this may either be a compensatory effect of decreased levels of interstitial 5-HT, an attempt to improve cognitive function, increase acetylcholine release or to counteract Aß accumulation.

AB - The 5-HT4 receptor may play a role in memory and learning and 5-HT4 receptor activation has been suggested to modulate acetylcholine release and to reduce amyloid-ß (Aß) accumulation. The aim of this study was for the first time to investigate the in vivo cerebral 5-HT4 receptor binding in early Alzheimer disease (AD) patients in relation to cortical Aß burden. Eleven newly diagnosed untreated AD patients (mean MMSE 24, range 19–27) and twelve age- and gender-matched healthy controls underwent a two-hour dynamic [11C]SB207145 PET scan to measure the binding potential of the 5-HT4 receptor. All AD patients and eight healthy controls additionally underwent a [11C]PIB PET scan to measure the cortical Aß burden. When AD patients were defined on clinical criteria, no difference in cerebral 5-HT4 receptor binding between AD patients and healthy controls was found (p = 0.54). However, when individuals were reassigned to groups according to their amyloid status, the PIB-positive individuals had 13% higher 5-HT4 receptor levels than PIB-negative individuals (p = 0.02) and the importance of classification of groups is emphasized. The 5-HT4 receptor binding was a positively correlated to Aß burden (p = 0.03) and negatively to MMSE score of the AD patients (p = 0.02). Our data suggests that cerebral 5-HT4 receptor upregulation starts at a preclinical stage of and continues while dementia is still at a mild stage, which contrasts other receptor subtypes. We speculate that this may either be a compensatory effect of decreased levels of interstitial 5-HT, an attempt to improve cognitive function, increase acetylcholine release or to counteract Aß accumulation.

U2 - 10.3233/JAD-2011-110056

DO - 10.3233/JAD-2011-110056

M3 - Journal article

C2 - 21673407

VL - 26

SP - 457

EP - 466

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 3

ER -