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

• Published in: Frontiers in cellular neuroscience Vol. 13; p. 538
• Main Authors: Metaxas, Athanasios, Thygesen, Camilla, Briting, Sanne R. R., Landau, Anne M., Darvesh, Sultan, Finsen, Bente
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 05.12.2019; Frontiers Media S.A
• Subjects: [3H]PK11195; [3H]UCB-J; Aging; Alzheimer's disease; Amyloid; Autopsy; Biomarkers; Brain research; Brodmann's area; Cloning; Cortex (frontal); Dementia; Dementia disorders; Frontal gyrus; Glycoproteins; Immunoglobulins; Immunohistochemistry; Inflammation; Medicine; Neurofibrillary tangles; Neuroimaging; neuroinflammation; Neuroscience; Neurosciences; Proteins; Senile plaques; Substantia grisea; synapses; Synaptic density; synaptic vesicle glycoprotein 2A; Tau protein; translocator protein; Denmark; Canada; Aarhus Denmark; amyloid; synapses; synaptic vesicle glycoprotein 2A; translocator protein; [3H]PK11195; [3H]UCB-J; neuroinflammation; tau
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2019.00538

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 ( = 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 [ H]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 [ H]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 [ H]PK11195, and negatively correlated with [ H]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.