Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 7, Pages 1675-1684Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3047-16.2016
Keywords
alpha-synuclein; dementia with Lewy bodies; hippocampus; memory; spread; subregion
Categories
Funding
- NIH/NIA Neuroplasticity of Aging Predoctoral Training Grant [2T32 AG00216-23]
- Shiley-Marcos Alzheimer's Disease Research Center (NIA Grant) [P50 AG05131]
- Helmsley Trust
- JPB Foundation
- Lookout Foundation
- Mathers Foundation
- NIH [AG18440]
Ask authors/readers for more resources
Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to alpha-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that alpha-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC -> CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1-the main output region for CA2-correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available