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Front Cell Neurosci. 2019 Dec 5;13:538. doi: 10.3389/fncel.2019.00538. eCollection 2019.

Increased Inflammation and Unchanged Density of Synaptic Vesicle Glycoprotein 2A (SV2A) in the Postmortem Frontal Cortex of Alzheimer's Disease Patients.

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Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.
Department of Nuclear Medicine and PET-Center, Aarhus University, Aarhus, Denmark.
Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
Department of Medicine, Neurology, and Geriatric Medicine, Dalhousie University, Halifax, NS, Canada.


Sections from the middle frontal gyrus (Brodmann area 46) of autopsy-confirmed Alzheimer's disease (AD) patients and non-demented subjects were examined for the prevalence of hallmark AD pathology, including amyloid-β (Aβ) plaques, phosphorylated tau (pTau) tangles, neuroinflammation and synaptic loss (n = 7 subjects/group). Dense-core deposits of Aβ were present in all AD patients (7/7) and some non-demented subjects (3/7), as evidenced by 6E10 immunohistochemistry. Levels of Aβ immunoreactivity were higher in AD vs. non-AD cases. For pTau, AT8-positive neurofibrillary tangles and threads were exclusively observed in AD patient tissue. Levels of [3H]PK11195 binding to the translocator protein (TSPO), a marker of inflammatory processes, were elevated in the gray matter of AD patients compared to non-demented subjects. Levels of [3H]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density, were not different between groups. In AD patients, pTau immunoreactivity was positively correlated with [3H]PK11195, and negatively correlated with [3H]UCB-J binding levels. No correlation was observed between Aβ immunoreactivity and markers of neuroinflammation or synaptic density. These data demonstrate a close interplay between tau pathology, inflammation and SV2A density in AD, and provide useful information on the ability of neuroimaging biomarkers to diagnose AD dementia.


[3H]PK11195; [3H]UCB-J; amyloid; neuroinflammation; synapses; synaptic vesicle glycoprotein 2A; tau; translocator protein

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