P4‐481: Association Between Entorhinal Cortical Tau Accumulation and Hippocampal Synaptic Density in Older Individuals With Normal Cognition and Early Alzheimer's Disease: Preliminary Experience
Year: 2019
Type: article
Abstract: Synaptic loss is a prominent AD pathology and the major structural correlate of cognitive impairment in AD. Positron emission tomography (PET) measurement of [C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) in early AD has demonstrated significant reductions (44%) in hippocampal synaptic density consistent with the early degeneration of entorhinal cortical (ERC) cells that project to the hippocampus. To assess the relationship between synaptic density and tau deposition, we performed PET imaging with [C]UCB-J and [F]flortaucipir and hypothesized that tau deposition in ERC (ERC-tau) would be inversely associated with synaptic density in the hippocampus. [C]UCB-J binding to SV2A and [F]flortaucipir binding to tau was measured in 9 AD and 5 cognitively normal (CN) participants. [C]UCB-J standardized uptake value ratios (SUVRs) from 40 to 60 min after injection were calculated in brain regions of interest (ROIs) using a whole cerebellum reference region and [F]flortaucipir binding to tau was calculated as SUVR from 80 to 100 min post-injection using an inferior cerebellum gray matter reference region. AD participants (68.8±1.1 years, CDR=0.5-1.0) ranged from amnestic mild cognitive impairment (n=5) to mild dementia (n=4). CN participants (76.8±5.2 years) were free of clinical symptoms (CDR=0). AD compared to CN participants demonstrated significant reductions in hippocampal [C]UCB-J binding (AD SUVR=0.81±0.13, CN SUVR=0.97±0.12, p=0.037) and significant increases in ERC [F]flortaucipir binding (CN SUVR=1.09±0.14, AD SUVR=1.57±0.18, p=0.0003). In the overall sample, higher ERC-tau was significantly associated with lower hippocampal synaptic density in the left hemisphere (r=−0.55, p=0.040) but not in the right hemisphere (r=−0.36, p=0.205), with a near-significant trend for the combined hemispheres (r=−0.52, p=0.059). The strength of these associations increased with normalization for ERC volume. As predicted, these preliminary imaging results revealed higher ERC-tau and lower hippocampal synaptic density in AD compared to CN participants. Consistent with our hypothesis, in the overall sample ERC-tau accumulation was associated with lower hippocampal synaptic density. This inverse association may reflect synaptic failure due to tau pathology in ERC neurons projecting to the hippocampus. However, further studies are needed to elucidate the relationship between tau accumulation and synaptic loss in AD.
Source: Alzheimer s & Dementia
Institutions: Yale University, Eli Lilly (United States)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980544642