TY - JOUR
T1 - Cerebral cortex pathology in aging and Alzheimer's disease
T2 - A quantitative survey of large hospital-based geriatric and psychiatric cohorts
AU - Giannakopoulos, Panteleimon
AU - Hof, Patrick R.
AU - Michel, Jean Pierre
AU - Guimon, José
AU - Bouras, Constantin
N1 - Funding Information:
This work was presented in partial fulfilment of the requirements for the habilitation degree of the first author submitted to the University of Geneva School of Medicine in 1997. We thank Drs. A. Delacourte and N.K. Robakis for generous gift of antibodies; Drs. P.G. Vallet, E. Kövari, F.R. Herrmann, G. Gold, L. Buée, V. Buée-Scherrer, E.A. Nimchinsky, J.C. Vickers, D.P. Perl and J.H. Morrison for participation in these studies and helpful discussion; and M. Surini and P.Y. Vallon for expert technical assistance. Supported by grants from the NIH (AG05138) and the Brookdale Foundation (to P.R.H.), and the Swiss National Science Foundation (Grants 3200-039767.93/1 and 31-45960.95 to C.B. and P.G., and fellowship Grant/1994 to P.G.).
PY - 1997/10
Y1 - 1997/10
N2 - In order to explore the relationships between the involvement of specific neuronal populations and cognitive deterioration, and to compare the hierarchical patterns of cortical involvement in normal brain aging and Alzheimer's disease, over 1200 brains from elderly subjects without cognitive deficits, as well as from patients with age-associated memory impairment and Alzheimer's disease, were examined. Our results suggest that the neuropathological changes associated with normal brain aging and Alzheimer's disease affect select cortical circuits at different points in time. Extensive hippocampal alterations are correlated with age-associated memory impairment, whereas substantial neurofibrillary tangle formation in neocortical association areas of the temporal lobe is a prerequisite for the development of Alzheimer's disease. Despite several lines of evidence involving amyloid deposit in the pathogenesis of Alzheimer's disease and Down's syndrome, our observations indicate that there is no correlation between senile plaque densities and degree of dementia in both disorders. In contrast to younger elderly cases, in the ninth and tenth decades of life, there is a differential cortical involvement in that parietal and cingulate areas are early affected in the course of Alzheimer's disease, and neocortical senile plaques densities are strongly correlated with the severity of dementia. Moreover, Alzheimer's disease symptomatology is characterized in these very old patients by high neurofibrillary tangle densities in the anterior CA1 field, but not in the entorhinal cortex and inferior temporal cortex. These observations are discussed in the light of the hypothesis of global corticocortical disconnection and with respect to the notion of selective neuronal vulnerability in Alzheimer's disease.
AB - In order to explore the relationships between the involvement of specific neuronal populations and cognitive deterioration, and to compare the hierarchical patterns of cortical involvement in normal brain aging and Alzheimer's disease, over 1200 brains from elderly subjects without cognitive deficits, as well as from patients with age-associated memory impairment and Alzheimer's disease, were examined. Our results suggest that the neuropathological changes associated with normal brain aging and Alzheimer's disease affect select cortical circuits at different points in time. Extensive hippocampal alterations are correlated with age-associated memory impairment, whereas substantial neurofibrillary tangle formation in neocortical association areas of the temporal lobe is a prerequisite for the development of Alzheimer's disease. Despite several lines of evidence involving amyloid deposit in the pathogenesis of Alzheimer's disease and Down's syndrome, our observations indicate that there is no correlation between senile plaque densities and degree of dementia in both disorders. In contrast to younger elderly cases, in the ninth and tenth decades of life, there is a differential cortical involvement in that parietal and cingulate areas are early affected in the course of Alzheimer's disease, and neocortical senile plaques densities are strongly correlated with the severity of dementia. Moreover, Alzheimer's disease symptomatology is characterized in these very old patients by high neurofibrillary tangle densities in the anterior CA1 field, but not in the entorhinal cortex and inferior temporal cortex. These observations are discussed in the light of the hypothesis of global corticocortical disconnection and with respect to the notion of selective neuronal vulnerability in Alzheimer's disease.
KW - Alzheimer's disease
KW - Amyloid
KW - Brain aging
KW - Centenarian
KW - Clinicopathologic correlation
KW - Hippocampus
KW - Neocortex
KW - Neurofibrillary tangle
UR - http://www.scopus.com/inward/record.url?scp=0030780381&partnerID=8YFLogxK
U2 - 10.1016/S0165-0173(97)00023-4
DO - 10.1016/S0165-0173(97)00023-4
M3 - Review article
C2 - 9403139
AN - SCOPUS:0030780381
SN - 0165-0173
VL - 25
SP - 217
EP - 245
JO - Brain Research Reviews
JF - Brain Research Reviews
IS - 2
ER -