Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment

  title={Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment},
  author={Robert D. Terry and Eliezer Masliah and David P. Salmon and Nelson M. Butters and Richard M. DeTeresa and Robert Hill and Lawrence A. Hansen and Robert Katzman.},
  journal={Annals of Neurology},
We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique… 

Alzheimer’s Disease and the Aging Brain

  • R. Terry
  • Biology, Psychology
    Journal of geriatric psychiatry and neurology
  • 2006
The frequencies of each of the several types of dementia are enumerated, showing that Alzheimer’s disease is present in about 80% of cases and the strongest structural correlate with cognitive tests is synapse loss, which is probably caused by Aβ oligopeptides in the terminal axons and dendrites.

Synaptic pathology in the pathogenesis of Alzheimer dementia

Data from a cohort of AD patients and other recent morphologic data do not support the hypothesis that amyloid deposition is a major pathogenic factor of both neuronal and synaptic loss in aging and AD.

Alzheimer's disease-related alterations in synaptic density: neocortex and hippocampus.

The ultrastructural studies assessing AD-related synaptic loss are reviewed and the possible compensatory changes in the synaptic complex that occur as a result of the loss in brain connectivity are reviewed.

Pathological substrates of cognitive decline in Alzheimer's disease.

The present review discusses the complex structure/function relationships in brain aging and AD within the theoretical framework of the functional neuropathology of brain aging.

Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease.

Data support the notion that neocortical neuronal degeneration, as indicated by NFT formation, is a critical determinant of the clinical progression of Alzheimer's disease and suggest that medial temporal lobe structures may represent the initial site of NFT Formation.

Correspondence amongst the PENO Test Battery Cognitive Results and Hippocampal Lesions in Alzheimer's Disease

The results strongly supported the use of the PENO battery test to evaluate the progression of cognitive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer’s disease.

Synaptic Pathology in Dementia

This chapter reviews and summarizes some of the morphological evidence for Alzheimer-related synaptic loss in the neocortex and hippocampus and suggests decline in synaptic plasticity may represent a loss of brain plasticity.

Altered synaptic function in Alzheimer's disease.

Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia.

The specificity of pathology in cortical vs subcortical locations for predicting a particular quality of neuropsychological deficit probably reflects disruption of corticocortical connections vs derangement of the basal forebrain cholinergic system.



Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity

The loss of neuronal connectivity, indexed by loss of synapses, predicted the degree of cognitive impairment in the patients who underwent biopsy and indicated a degree of structural change in AD brain not likely to be affected by pharmacotherapy.

Plaques, tangles and dementia A quantitative study

Lateralization of brain morphologic and cholinergic abnormalities in Alzheimer's disease.

Left- right asymmetry in the density of senile plaques diminished with increasing neuropathologic severity, while similar evidence for diminishing left-right asymmetry of neurofibrillary tangle density or cholinergic enzyme activity with increasing severity was not found.

Some morphometric aspects of the brain in senile dementia of the alzheimer type

Image analysis apparatus was used to count and measure glial and neuronal perikarya in ten size classes in the midfrontal region and superior temporal gyrus of 18 patients with senile dementia of the

Plasticity of hippocampal circuitry in Alzheimer's disease.

Results are evidence that the central nervous system is capable of a plastic response in Alzheimer's disease, and adaptive growth responses occur along with the degenerative events.

Senile Dementia of the Alzheimer Type Without Neocortical Neurofibrillary Tangles

It is concluded that SDAT with neocortical NFT is the same disease as SDAT without them, although the presence of such tangles is associated with a tendency towards greater severity.

Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease.

A peptide derived from the amyloid precursor may be neurotoxic, and conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against theAmyloid polypeptide.

Longitudinal evaluation of dementia of the Alzheimer type

Of the 3 commonly employed tests of mental status, only the DRS evidenced greater to change with increasing dementia severity, suggesting that a patient's rate of progression in 1 year may bear little relationship to future rate of decline.

The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects

The expectation of mental disorder shows a steep increase with advancing chronological age, and beyond 75 years a large part of this increase is accounted for by disorders associated with degenerative changes in the central nervous system for which the authors lack remedies at the present time.