Cited by 177Alzheimer's disease research and treatmentsMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

Reinnervation of the hippocampal perforant pathway zone in Alzheimer's disease

Hyman, B. T., Kromer, L. J., van Hoesen, G. W.·1987·Annals of Neurology

Abstract

The perforant pathway originates from the entorhinal cortex of the anterior parahippocampal gyrus and terminates on the outer dendritic branches of the granule cells of the dentate gyrus and pyramidal cells of the subiculum and hippocampus. It carries the principal cortical input to the hippocampal formation. Destruction of the perforant pathway in experimental animals leads to a partial deafferentation of its target neurons, followed by a robust sprouting of acetylcholinesterase (AChE) terminals in the deafferented perforant pathway zone. In Alzheimer's disease, the cells of origin of the perforant pathway are laden with neurofibrillary tangles. AChE staining in the terminal zone of the perforant pathway in Alzheimer's disease shows several distinct patterns that are not found in control brains. These changes are consistent with the results of experimental studies demonstrating reinnervation in laboratory mammals, including nonhuman primates. The results suggest that in Alzheimer's disease sprouting of AChE-containing systems occurs in the hippocampal formation in response to disease-related cellular damage in the entorhinal cortex.

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Crossref · 10.1002/ana.410210307

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  • The first neurons affected in Alzheimer disease are layer II entorhinal cortex neurons that give rise to the perforant pathway.

    “The first neurons to be affected are in layer II of entorhinal cortex (EC), the neurons that give rise to the perforant pathway, the single major projection linking the cerebral cortex with the hippocampus (Gomez-Isla et al., 1996; Hyman et al., 1987).”

    From Propagation of Tau Pathology in a Model of Early Alzheimer's Disease (2012) · cites this paper as Hyman et al., 1987

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Authors
Hyman, B. T., Kromer, L. J., & van Hoesen, G. W.
Affiliations
University of Iowa (US)
Venue
Annals of Neurology
Publisher
Wiley
Published
1987-03
Volume
21
Issue
3
Pages
259-267
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2142746788
Cited by
177
References
44
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 4
FWCI
11.44
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (P0 NS 19632, NS-14944)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
perforant path, Alzheimer's disease, reinnervation, acetylcholinesterase, entorhinal cortex, deafferentation, neurofibrillary tangles, dentate gyrus, subiculum, hippocampal formation, cholinergic nerve terminals, sprouting
MeSH terms
Acetylcholinesterase, Aged, Aged, 80 and over, Alzheimer Disease, Hippocampus, Histocytochemistry, Humans, Limbic System, Neural Pathways, Neurofibrils, Neuronal Plasticity

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