PMID- 8699259
OWN - NLM
STAT- MEDLINE
DCOM- 19960830
LR  - 20220410
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 16
IP  - 14
DP  - 1996 Jul 15
TI  - Profound loss of layer II entorhinal cortex neurons occurs in very mild 
      Alzheimer's disease.
PG  - 4491-500
AB  - 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.
FAU - Gomez-Isla, T
AU  - Gomez-Isla T
AD  - Neurology Service, Massachusetts General Hospital, Boston 02114, USA.
FAU - Price, J L
AU  - Price JL
FAU - McKeel, D W Jr
AU  - McKeel DW Jr
FAU - Morris, J C
AU  - Morris JC
FAU - Growdon, J H
AU  - Growdon JH
FAU - Hyman, B T
AU  - Hyman BT
LA  - eng
GR  - AG03991/AG/NIA NIH HHS/United States
GR  - R01 AG008487/AG/NIA NIH HHS/United States
GR  - P01 AG003991/AG/NIA NIH HHS/United States
GR  - P50 AG005681/AG/NIA NIH HHS/United States
GR  - P50 AG005134/AG/NIA NIH HHS/United States
GR  - AG05134/AG/NIA NIH HHS/United States
GR  - AG08487/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*pathology
MH  - Cell Death
MH  - Entorhinal Cortex/*pathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
PMC - PMC6578866
EDAT- 1996/07/15 00:00
MHDA- 2001/03/28 10:01
PMCR- 1997/01/15
CRDT- 1996/07/15 00:00
PHST- 1996/07/15 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1996/07/15 00:00 [entrez]
PHST- 1997/01/15 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.16-14-04491.1996 [doi]
PST - ppublish
SO  - J Neurosci. 1996 Jul 15;16(14):4491-500. doi: 10.1523/JNEUROSCI.16-14-04491.1996.