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61/100

✓ Peer-reviewed alzhub usefulness score 61 out of 100. Getting a diagnosis

Topic: Brain proteins, microglia and lab models

The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC gives rise to the perforant pathway, the major source of the excitatory input to the hippocampus, and layer IV receives a major hippocampal efferent projection. The EC is affected severely in Alzheimer disease (AD), likely contributing to memory impairment. We applied stereological principles of neuron counting to determine whether neuronal loss occurs in the EC in the very early stages of AD. We studied 20 individuals who at death had a Clinical Dementia Rating (CDR) score of 0 (cognitively normal), 0.5 (very mild), 1 (mild), or 3 (severe cognitive impairment). Lamina-specific neuronal counts were carried out on sections representing the entire EC. In the cognitively normal (CDR = 0) individuals, there were approximately 650,000 neurons in layer II, 1 million neurons in layer IV, and 7 million neurons in the entire EC. The number of neurons remained constant between 60 and 90 years of age. The group with the mildest clinically detectable dementia (CDR = 0.5), all of whom had sufficient neurofibrillary tangles (NFTs) and senile plaques for the neuropathological diagnosis of AD, had 32% fewer EC neurons than controls. Decreases in individual lamina were even more dramatic, with the number of neurons in layer II decreasing by 60% and in layer IV by 40% compared with controls. In the severe dementia cases (CDR = 3), the number of neurons in layer II decreased by approximately 90%, and the number of neurons in layer IV decreased by approximately 70% compared with controls. Neuronal number in AD was inversely proportional to NFT formation and neuritic plaques, but was not related significantly to diffuse plaques or to total plaques. These results support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Gómez-Isla, T., Price, J. L., McKeel, D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996). Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.16-14-04491.1996

Vancouver

Gómez-Isla T, Price JL, McKeel DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. 1996. doi:10.1523/jneurosci.16-14-04491.1996. PMID: 8699259.

BibTeX

@article{gomezisla1996-8699259,
  author  = {Gómez-Isla, T. and Price, J. L. and McKeel, D. W. and Morris, J. C. and Growdon, J. H. and Hyman, B. T.},
  title   = {{Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease}},
  journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year    = {1996},
  doi     = {10.1523/jneurosci.16-14-04491.1996},
  pmid    = {8699259},
  url     = {https://doi.org/10.1523/jneurosci.16-14-04491.1996}
}

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Key findings

Decreases in individual lamina were even more dramatic, with the number of neurons in layer II decreasing by 60% and in layer IV by 40% compared with controls.
In the severe dementia cases (CDR = 3), the number of neurons in layer II decreased by approximately 90%, and the number of neurons in layer IV decreased by approximately 70% compared with controls.
Neuronal number in AD was inversely proportional to NFT formation and neuritic plaques, but was not related significantly to diffuse plaques or to total plaques.
These results support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging.

Why it matters

In this study of 20 brains examined after death, people with the very mildest clinically detectable dementia (CDR 0.5) had 60% fewer layer II neurons in the entorhinal cortex — a gateway to the brain's memory hub — than cognitively normal people, whose counts stayed constant from age 60 to 90; in severe dementia the loss was about 90%. Neuron loss tracked tangles and neuritic plaques but not diffuse plaques, and the authors say this "distinguishes even very mild AD from nondemented aging." All the very mild cases already had enough tangles and plaques for an AD diagnosis, so the study shows how early the damage is found, not what causes it — and it tests no treatment.

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Study details

Participants20
Evidence strengthLow

How this study scored 61/100

Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience)
Journal's citation record	4 / 4	Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	1996 — older than 20 years, still counted
Sample size	1 / 4	20 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	7 / 7	Cited 1,804 times (OpenAlex, 2026-10-10)
Citations per year	5 / 5	56.4 citations a year over 32 year(s) since 1996
Impact for its field and year	6 / 6	Cited 43.7× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	4 / 6	Cited by 87 other studies in this library
Still being cited	3 / 4	Cited 158 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Bradley T. Hyman: h-index 190 (OpenAlex, whole career)
Institution's track record	2 / 3	Massachusetts General Hospital: institution h-index 2,057 (OpenAlex)
Multicenter collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 8699259)
Free to read	0 / 2	Behind a paywall — scores zero
Total	61 / 100	—

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