Perforant pathway changes and the memory impairment of Alzheimer's disease

Hyman, B. T.; Van Hoesen, G. W.; Kromer, L. J.; Damasio, A. R.

doi:10.1002/ana.410200406

Cited by 672Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMemory and Neural Mechanisms

Perforant pathway changes and the memory impairment of Alzheimer's disease

Hyman, B. T., Van Hoesen, G. W., Kromer, L. J., Damasio, A. R.·1986·Annals of Neurology

DOI 10.1002/ana.410200406

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Abstract

The perforant pathway is a large neuronal projection that arises from layers II and III of the entorhinal cortex of the parahippocampal gyrus. It is the principal source of cortical input to the hippocampal formation. In 11 cases of Alzheimer's disease, we have found that neurofibrillary tangles develop in the cells of origin of the perforant pathway. In addition, the termination zone of the perforant pathway, in the outer two thirds of the molecular layer of the dentate gyrus, contains a distinct layer of neuritic plaques. None of the 8 control subjects had such changes. These profound alterations effectively disconnect the hippocampal formation from the association and limbic cortices. Because of the central role of the hippocampus and parahippocampal gyrus in learning, it is likely that pathological changes in the perforant pathway, by precluding normal hippocampal operation, account for some aspects of the memory impairment in Alzheimer's disease.

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According to Hyman et al., episodic memory deficit in AD results from anatomical and functional segregation of hippocampus from associative sensory inputs due to degeneration of perforant pathway.
“Indeed, according to Hyman et al. [29], [30], the episodic memory deficit in AD patients results from the anatomical and functional segregation of the hippocampus from associative sensory inputs due to degeneration of the perforant pathway.”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [30]

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Authors: Hyman, B. T., Van Hoesen, G. W., Kromer, L. J., & Damasio, A. R.
Affiliations: University of Iowa (US)
ORCID: Hyman, B. T.
Venue: Annals of Neurology
Publisher: Wiley
Published: 1986-10
Volume: 20
Issue: 4
Pages: 472-481
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.410200406
OpenAlex: W2071006250
Semantic Scholar: 49ebc7ed6030722a2591af7a320ec2c950fe0271
Cited by: 672
References: 68
Citations by year: 2026: 6 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 14 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 8 · 2014: 8 · 2013: 16 · 2012: 9
FWCI: 23.69
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 6582 d)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Eye Institute (1F32EY5720)
National Institute of Neurological Disorders and Stroke (P0 NS 19632, NS-14944)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: perforant path, Alzheimer's disease, memory impairment, entorhinal cortex, parahippocampal gyrus, hippocampal formation, neurofibrillary tangles, neuritic plaques, dentate gyrus
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Dementia, Hippocampus, Humans, Limbic System, Memory Disorders, Middle Aged, Neural Pathways, Neurofibrils

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Perforant pathway changes and the memory impairment of Alzheimer's disease

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