Synaptic vesicle glycoprotein 2A (SV2A) levels in the cerebral cortex in patients with Alzheimer's disease: a radioligand binding study in postmortem brains
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Synaptic vesicle glycoprotein 2A (SV2A) levels in the cerebral cortex in patients with Alzheimer's disease : a radioligand binding study in postmortem brains. / Mikkelsen, Jens D.; Kaad, Sif; Aripaka, Sanjay S.; Finsen, Bente.
In: Neurobiology of Aging, Vol. 129, 2023, p. 50-57.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synaptic vesicle glycoprotein 2A (SV2A) levels in the cerebral cortex in patients with Alzheimer's disease
T2 - a radioligand binding study in postmortem brains
AU - Mikkelsen, Jens D.
AU - Kaad, Sif
AU - Aripaka, Sanjay S.
AU - Finsen, Bente
N1 - Publisher Copyright: © 2023 Elsevier Inc.
PY - 2023
Y1 - 2023
N2 - Histological and biochemical analyses in postmortem tissues have demonstrated neurodegenerative changes in the cerebral cortex in patients with Alzheimer's disease (AD), and it has been suggested that this represents a loss of synapses. PET imaging of the (pre)synaptic vesicular glycoprotein 2A (SV2A) has demonstrated a reduction in synapse density in AD in the hippocampus but not consistently in the neocortex. This investigation examines the level of [3H]UCB-J binding in postmortem cortical tissue from patients with AD and matched healthy controls using autoradiography. Among the neocortical areas examined, the binding was significantly lower only in the middle frontal gyrus in AD compared to matched controls. No differences were observed in the parietal, temporal, or occipital cortex. The binding levels in the frontal cortex in the AD cohort displayed large variability among subjects, and this revealed a highly significant negative association with the age of the patient. These results demonstrate low UCB-J binding in the frontal cortex of patients with AD, and this biomarker correlates negatively with age, which may further indicate that SV2A could be an important biomarker in AD patients.
AB - Histological and biochemical analyses in postmortem tissues have demonstrated neurodegenerative changes in the cerebral cortex in patients with Alzheimer's disease (AD), and it has been suggested that this represents a loss of synapses. PET imaging of the (pre)synaptic vesicular glycoprotein 2A (SV2A) has demonstrated a reduction in synapse density in AD in the hippocampus but not consistently in the neocortex. This investigation examines the level of [3H]UCB-J binding in postmortem cortical tissue from patients with AD and matched healthy controls using autoradiography. Among the neocortical areas examined, the binding was significantly lower only in the middle frontal gyrus in AD compared to matched controls. No differences were observed in the parietal, temporal, or occipital cortex. The binding levels in the frontal cortex in the AD cohort displayed large variability among subjects, and this revealed a highly significant negative association with the age of the patient. These results demonstrate low UCB-J binding in the frontal cortex of patients with AD, and this biomarker correlates negatively with age, which may further indicate that SV2A could be an important biomarker in AD patients.
KW - Aging
KW - Alzheimer's disease
KW - Autoradiography
KW - Frontal cortex
KW - SV2A
U2 - 10.1016/j.neurobiolaging.2023.05.003
DO - 10.1016/j.neurobiolaging.2023.05.003
M3 - Journal article
C2 - 37269646
AN - SCOPUS:85160558635
VL - 129
SP - 50
EP - 57
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -
ID: 359241236