Cited by 449Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMemory and Neural Mechanisms

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Memory‐related neural systems in Alzheimer's disease: An anatomic study

Hyman, B. T., Hoesen, G. W. Van, Damasio, A. R.·1990·Neurology

DOI 10.1212/wnl.40.11.1721

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Abstract

In the primate brain, there are strong connections among the entorhinal cortex, the hippocampal formation, and the amygdala, 3 structures of the ventromedial temporal lobe that are related to memory function. Because memory impairment is a central feature of Alzheimer's disease, we examined the probable cells of origin and terminal zones of these connections in the brains of humans affected by the disease, using thioflavine S, Alz-50, and anti-A4 amyloid protein immunocytochemistry. Specific cytoarchitectural areas and lamina that give rise to projections from the entorhinal cortex, the hippocampal formation, and the amygdala consistently contained neurofibrillary tangles. The terminal zones of many of these projections contained neuritic plaques, Alz-50-positive neuritic alterations, and A4 deposition. Other cytoarchitectural areas and lamina, sometimes immediately adjacent, were consistently spared from these Alzheimer changes. This pattern of Alzheimer-related alterations would disrupt projections among the entorhinal cortex, hippocampal formation, and amygdala at multiple sites, and also disrupt projections between these structures and cortical and subcortical targets. In functional terms, this pattern of structural damage is likely to be as devastating as bilateral destruction of the ventromedial temporal lobe, and thus contribute substantially to the memory disorder seen in this condition.

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“…neurons may result in disconnection and deafferentation of critical neural communication between the presubiculum and parieto-occipital cortex and thus is likely to (Duyckaerts, Delatour, & Potier, 2009; Hyman, Hoesen, & Damasio, 1990) contribute to the defects in attention in patients with c-MCI.”
Relationship between a novel learning slope metric and Alzheimer’s disease biomarkers
Hammers, D. B., Suhrie, K. R., Dixon, A. M., Gradwohl, B. D., Archibald, Z. G., King, J. B., Spencer, R. J., Duff, K. M., & Hoffman, J. M. (2021) · Aging Neuropsychology and Cognition · doi:10.1080/13825585.2021.1919984 · Cited by 18
“…with the preponderance of research suggesting that early and predominant anterograde episodic/semantic memory deficits are a hallmark cognitive marker of AD due to entorhinal cortex and hippocampal/medial temporal lobe degeneration (Braak & Braak, 1991; Hyman et al., 1990; Van Hoesen et al., 1991).”
Background
Negative Emotional Verbal Memory Biases in Mild Cognitive Impairment and Late-Onset Depression
Mah, L., Anderson, N. D., Verhoeff, N. P. L. G., & Pollock, B. G. (2017) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.05.005 · Cited by 20
Connections and Cognitive Impairment in Alzheimer’s Disease
Gómez‐Isla, T., & Hyman, B. T. (1997) · Springer eBooks · doi:10.1007/978-3-642-60680-9_11 · Cited by 18
Self-citation
The Hippocampal Subfield Volume Reduction and Plasma Biomarker Changes in Mild Cognitive Impairment and Alzheimer’s Disease
Cao, J., Tang, Y., Chen, S., Yu, S., Wan, K., Yin, W., Zhen, W., Zhao, W., Zhou, X., Zhu, X., et al. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231114 · Cited by 17
Sequence and trajectory of early Alzheimer’s disease-related tau inclusions in the hippocampal formation of cases without amyloid-β deposits
Braak, H., Mayer, B., Feldengut, S., Schön, M., & Tredici, K. D. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02862-x · Cited by 20
Talsaclidine (WAL 2014 FU), a muscarinic M1 receptor agonist for the treatment of Alzheimer's disease
Wienrich, M., Ceci, A., Ensinger, H. A., Gaida, W., Mendla, K. D., Osugi, T., Raschig, A., & Weiser, T. W. (2002) · Drug Development Research · doi:10.1002/ddr.10085 · Cited by 17
Glycogen synthase kinase 3α and 3β do not colocalize with neurofibrillary tangles
Harr, S. D., Hollister, R., & Hyman, B. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00025-5 · Cited by 16
Self-citation
Neuropathology of Alzheimer’s Disease
Schultz, C., Del Tredici, K., & Braak, H. (2004) · Alzheimer’s Disease · doi:10.1007/978-1-59259-661-4_2 · Cited by 28
Post-Training Memory Processing in Amygdala, Septum and Hippocampus: Role of Benzodiazepine/GABAA Receptors, and their Interaction with other Neurotransmitter Systems
Izquierdo, I., Medina, J. H., Jeriisalinsky, D., & Cunha, C. D. (1992) · Reviews in the Neurosciences · doi:10.1515/revneuro.1992.3.1.11 · Cited by 16
Superior Longitudinal Fasciculus and Arcuate Fasciculus
Schmahmann, J. D., & Pandya, D. Ν. (2006) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195104233.003.0013 · Cited by 19
Preliminary Validation of the Learning Ratio for the HVLT–R and BVMT–R in Older Adults
Hammers, D. B., Gradwohl, B. D., Kucera, A., Abildskov, T. J., Wilde, E. A., & Spencer, R. J. (2021) · Cognitive and Behavioral Neurology · doi:10.1097/wnn.0000000000000277 · Cited by 16
Comparison of temporal order memory in early and middle stage Alzheimer's disease
Johnson, D. L., & Kesner, R. P. (1997) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688639708403839 · Cited by 16
A brief computerized self-screen for dementia
Kluger, B. M., Saunders, L. V., Hou, W., GARVAN, C. W., Kirli, S., Efros, D. B., Chau, Q.-A. N., Crucian, G. P., Finney, G. R., Meador, K. J., et al. (2008) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390802317559 · Cited by 16
“AD patients, early in their course of disease, often demonstrate pathological changes in their entorhinal cortex (Hyman, Van Hoesen, & Damasio, 1990).”
Background
Glial reaction in aging and Alzheimer's disease
Unger, J. W. (1998) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19981001)43:1 · Cited by 103
Cognitive effects of Colostral-Val nonapeptide in aged rats
Popik, P., Galoch, Z., Janusz, M., Lisowski, J., & Vetulani, J. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00323-5 · Cited by 16
“Pathophysiological changes in Alzheimer’s patients include, among others, accumulation of b-amyloid plaques and neurofibrillary tangles [12].”
Background
Aspects of Cortical Destruction in Alzheimer’s Disease
Braak, H., & Braak, E. (1997) · Springer eBooks · doi:10.1007/978-3-642-60680-9_1 · Cited by 17
No spatial working memory deficit in β-amyloid-exposed rats
Roloff, E. V. L., Platt, B., & Riedel, G. (2002) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(02)00211-7 · Cited by 17
“Such degeneration first appears in brain regions that compose parts of the medial temporal lobe and include both the hippocampus and amygdala (Hyman et al., 1990).”
Background
Remodeling of projections from ventral hippocampus to prefrontal cortex in Alzheimer's mice
Xu, F., Ono, M., Ito, T., Uchiumi, O., Wang, F., Zhang, Y., Sun, P., Zhang, Q., Yamaki, S., Yamamoto, R., et al. (2020) · The Journal of Comparative Neurology · doi:10.1002/cne.25032 · Cited by 15
The neuroprotective role of Nigella sativa extract on ciprofloxacin and pentylenetetrazole treated rats
Abdel-Rahman, M. (2013) · African Journal of Pharmacy and Pharmacology · doi:10.5897/ajpp12.897 · Cited by 15
“In addition, there are connections between striatum and hippocampus via the entorhinal and prefrontal cortex (Hyman et al. 1990; Christakou et al., 2004).”
Background

Authors: Hyman, B. T., Hoesen, G. W. V., & Damasio, A. R.
Affiliations: University of Iowa (US)
ORCID: Hyman, B. T.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1990-11
Volume: 40
Issue: 11
Pages: 1721-1721
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.40.11.1721
OpenAlex: W2160683996
Cited by: 449
References: 0
Citations by year: 2025: 4 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 10 · 2014: 5 · 2013: 7 · 2012: 7
FWCI: 16.38
Type: journal article
Language: en
Open access: closed
Locations: Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG-08487)
National Institute of Neurological Disorders and Stroke (P0 NS 19632, R01NS014944, NS-14944)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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: Alzheimer's disease, memory impairment, entorhinal cortex, hippocampal formation, amygdala, neurofibrillary tangles, neuritic plaques, thioflavine S
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Amygdala, Brain, Hippocampus, Humans, Immunohistochemistry, Memory, Middle Aged, Neurofibrils, Temporal Lobe

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Memory‐related neural systems in Alzheimer's disease: An anatomic study

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