Cerebral cortex pathology in aging and Alzheimer's disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts

Giannakopoulos, Pantéleimon; Hof, Patrick R.; Michel, Jean‐Pierre; Guimón, José; Bouras, Constantin

doi:10.1016/s0165-0173(97)00023-4

Cited by 167 publications

(92 citation statements)

References 196 publications

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“…These observations are also consistent with the differential degrees of atrophy as revealed by assessing cortical volumes even in the frontal lobe in Alzheimer's disease (Halliday et al, 2003). However, while neurofibrillary pathology (AT8 and amyloid-b immunoreactivites) could have influenced neuronal size (Giannakopoulos et al, 1997), it is plausible that the observed atrophic changes in the dorsolateral PFC result from different pathogenetic mechanisms not withstanding changes in intracellular regulatory proteins within different organelles or nuclei (Salehi et al, 1996;Love et al, 1999). It has been suggested that the brain has a limited repertoire to insults, with pathologies from unrelated aetiologies displaying similar end stage changes (Wardlaw et al, 2003).…”

Section: Discussionsupporting

confidence: 83%

Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias

Foster

Oakley

Slade

et al. 2014

Brain

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Dementia associated with cerebrovascular disease is common. It has been reported that $30% of elderly patients who survive stroke develop delayed dementia (post-stroke dementia), with most cases being diagnosed as vascular dementia. The pathological substrates associated with post-stroke or vascular dementia are poorly understood, particularly those associated with executive dysfunction. Three separate yet interconnecting circuits control executive function within the frontal lobe involving the dorsolateral prefrontal cortex, anterior cingulate cortex and the orbitofrontal cortex. We used stereological methods, along with immunohistological and related cell morphometric analysis, to examine densities and volumes of pyramidal neurons of the dorsolateral prefrontal cortex, anterior cingulate cortex and orbitofrontal cortex in the frontal lobe from a total of 90 elderly subjects (age range 71-98 years). Post-mortem brain tissues from post-stroke dementia and post-stroke patients with no dementia were derived from our prospective Cognitive Function After Stroke study. We also examined, in parallel, samples from ageing controls and similar age subjects pathologically diagnosed with Alzheimer's disease, mixed Alzheimer's disease and vascular dementia, and vascular dementia. We found pyramidal cell volumes in layers III and V in the dorsolateral prefrontal cortex of post-stroke and vascular dementia and, of mixed and Alzheimer's disease subjects to be reduced by 30-40% compared to post-stroke patients with no dementia and controls. There were no significant changes in neuronal volumes in either the anterior cingulate or orbitofrontal cortices. Remarkably, pyramidal neurons within the orbitofrontal cortex were also found to be smaller in size when compared to those in the other two neocortical regions. To relate the cell changes to cognitive function, we noted significant correlations between neuronal volumes and total CAMCOG, orientation and memory scores and clinical dementia ratings. Total estimated neuronal densities were not significantly changed between patients with post-stroke dementia and post-stroke patients with no dementia groups or ageing controls in any of the three frontal regions. In further morphometric analysis of the dorsolateral prefrontal cortex, we showed that neither diffuse cerebral atrophy nor neocortical thickness explained the selective neuronal volume effects. We also noted that neurofilament protein SMI31 immunoreactivity was increased in post-stroke and vascular dementia compared with post-stroke patients with no dementia and correlated with decreased neuronal volumes in subjects with post-stroke dementia and vascular dementia. Our findings suggest selective regional pyramidal cell atrophy in the dorsolateral prefrontal cortex-rather than neuronal density changes per se-are associated with dementia and executive dysfunction in poststroke dementia and vascular dementia. The changes in dorsolateral prefrontal cortex pyramidal cells were not associated with neurofibrillary pathology suggesting...

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Section: Discussionsupporting

confidence: 83%

Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias

Foster

Oakley

Slade

et al. 2014

Brain

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“…The suggestion that brain Aβ accumulation and neurodegeneration are correlated remains an area of contention. Studies of human brain extracts and transgenic mice suggest such a correlation does not exist (13,14), whereas other studies support this relationship (15). Amyloid deposition in the brain does correlate with progress from mild cognitive impairment to AD (16).…”

mentioning

confidence: 95%

High-speed atomic force microscopy reveals structural dynamics of amyloid β _1–42 aggregates

Watanabe‐Nakayama

Ono

Itami

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

223

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Aggregation of amyloidogenic proteins into insoluble amyloid fibrils is implicated in various neurodegenerative diseases. This process involves protein assembly into oligomeric intermediates and fibrils with highly polymorphic molecular structures. These structural differences may be responsible for different disease presentations. For this reason, elucidation of the structural features and assembly kinetics of amyloidogenic proteins has been an area of intense study. We report here the results of high-speed atomic force microscopy (HS-AFM) studies of fibril formation and elongation by the 42-residue form of the amyloid β-protein (Aβ1–42), a key pathogenetic agent of Alzheimer's disease. Our data demonstrate two different growth modes of Aβ1–42, one producing straight fibrils and the other producing spiral fibrils. Each mode depends on initial fibril nucleus structure, but switching from one growth mode to another was occasionally observed, suggesting that fibril end structure fluctuated between the two growth modes. This switching phenomenon was affected by buffer salt composition. Our findings indicate that polymorphism in fibril structure can occur after fibril nucleation and is affected by relatively modest changes in environmental conditions.

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“…In particular, it has remained unclear whether A␤ and/or its deposition in the parenchyma is the cause of the nerve cell loss. Whereas older studies report a poor correlation between dementia and amyloid plaques (Gomez-Isla et al, 1996b;Giannakopoulos et al, 1997), more recent studies have found stronger correlations between either total A␤ load or neuritic A␤ plaques and nerve cell loss and/or dementia (Cummings and Cotman, 1995;Knowles et al, 1998;Naslund et al, 2000).…”

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confidence: 99%

Amyloid-Associated Neuron Loss and Gliogenesis in the Neocortex of Amyloid Precursor Protein Transgenic Mice

et al. 2002

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APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. We have previously reported neuron loss in the hippocampal CA1 region of 14-to 18-month-old APP23 mice. In contrast, no neuron loss was found in neocortex. In the present study we have reinvestigated neocortical neuron numbers in adult and aged APP23 mice. Surprisingly, results revealed that 8-month-old APP23 mice have 13 and 14% more neocortical neurons compared with 8-month-old wild-type and 27-month-old APP23 mice, respectively. In 27-month-old APP23 mice we found an inverse correlation between amyloid load and neuron number. These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. Supporting this notion, we found more neurons with a necroticapoptotic phenotype in the neocortex of 24-month-old APP23 mice compared with age-matched wild-type mice. Stimulated by recent reports that demonstrated neurogenesis after targeted neuron death in the mouse neocortex, we have also examined neurogenesis in APP23 mice. Strikingly, we found a fourfold to sixfold increase in newly produced cells in 24-month-old APP23 mice compared with both age-matched wildtype mice and young APP23 transgenic mice. However, subsequent cellular phenotyping revealed that none of the newly generated cells in neocortex had a neuronal phenotype. The majority were microglial and to a lesser extent astroglial cells. We conclude that cerebral amyloidosis in APP23 mice causes a modest neuron loss in neocortex and induces marked gliogenesis.

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Cerebral cortex pathology in aging and Alzheimer's disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts

Cited by 167 publications

References 196 publications

Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias

Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias

High-speed atomic force microscopy reveals structural dynamics of amyloid β _1–42 aggregates

Amyloid-Associated Neuron Loss and Gliogenesis in the Neocortex of Amyloid Precursor Protein Transgenic Mice

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Cerebral cortex pathology in aging and Alzheimer's disease: a quantitative survey of large hospital-based geriatric and psychiatric cohorts

Cited by 167 publications

References 196 publications

Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias

Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias

High-speed atomic force microscopy reveals structural dynamics of amyloid β 1–42 aggregates

Amyloid-Associated Neuron Loss and Gliogenesis in the Neocortex of Amyloid Precursor Protein Transgenic Mice

Contact Info

Product

Resources

About

High-speed atomic force microscopy reveals structural dynamics of amyloid β _1–42 aggregates