Neuron Number in the Entorhinal Cortex and CA1 in Preclinical Alzheimer Disease

Price, Joseph L.; Ko, Anthony; Wade, Marcus J.; Tsou, Sarah K.; McKeel, Daniel W.; Morris, John C.

doi:10.1001/archneur.58.9.1395

Cited by 518 publications

(399 citation statements)

References 46 publications

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“…Neurons are lost from the entorhinal cortex already in very mild stages of Alzheimer's disease [16,49]. The latter study also shows a reduction of CA1 neurons in very mild and severe Alzheimer's disease, but not in nondemented healthy subjects of 60-89 years of age and in preclinical Alzheimer's disease cases [49]. Furthermore, the neuron loss in CA1 seemed to uniquely predict the duration and severity of Alzheimer's disease [8].…”

Section: Discussionmentioning

confidence: 66%

“…In fact, Simic et al [55] might have included early undiagnosed cases of Alzheimer's disease in the study on the effects of normal human aging [47]. Neurons are lost from the entorhinal cortex already in very mild stages of Alzheimer's disease [16,49]. The latter study also shows a reduction of CA1 neurons in very mild and severe Alzheimer's disease, but not in nondemented healthy subjects of 60-89 years of age and in preclinical Alzheimer's disease cases [49].…”

Section: Discussionmentioning

confidence: 99%

“…With stereological techniques, several studies provided evidence that neurons in layer II of the entorhinal cortex do not disappear in the aging rhesus monkey [14,35,46,65], or in other entorhinal cortical layers of the nonhuman primate [35,46]. Also in cognitively normal human subjects, stereological analyses showed that neuron numbers in entorhinal cortical layers II, III, IV, or V/VI remained constant between 60 and 90 years of age [16,49].…”

Section: Discussionmentioning

confidence: 99%

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Preservation of hippocampal neuron numbers in aged rhesus monkeys

Keuker

Luiten

Fuchs

2003

Neurobiology of Aging

122

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Preservation of hippocampal neuron numbers in aged rhesus monkeys Keuker, J.I.H.; Luiten, P.G.M.; Fuchs, E. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractTo investigate whether or not aging of nonhuman primates is accompanied by a region-specific neuron loss in the hippocampal formation, we used the optical fractionator technique to obtain stereological estimates of unilateral neuron numbers of the hippocampi of eight young (0-4 years) and five aged (18-31 years) male rhesus monkeys (Macaca mulatta). Our results show a preservation of neurons (mean × 10 3 ± S.D. × 10 3 ) in the subiculum (young = 588 ± 124, aged = 612 ± 207), CA1 (young = 1051 ± 249, aged = 1318 ± 311), CA2 (young = 100 ± 18, aged = 113 ± 12), CA3 (young = 478 ± 125, aged = 509 ± 139), hilus (young = 337 ± 115, aged = 394 ± 90), and dentate gyrus (young = 5550 ± 1725, aged = 7799 ± 2087) of the hippocampal formation. These results confirm a previous stereological study in rhesus monkeys, but are in conflict with data for humans, showing age-dependent region-specific alterations in the hippocampal formation.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Keuker

Luiten

Fuchs

2003

Neurobiology of Aging

122

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“…There is some, but still very limited, evidence that neuron loss may be more pronounced and neurofibrillary tangles may be more frequent in amygdala than in hippocampus in early stages of AD [2,20,33,34,43,47,52]. This may indicate more rapid progression or earlier onset of pathological changes in amygdala than hippocampus so that amygdala atrophy may have reached its maximum even before the conversion from MCI to AD.…”

Section: Discussionmentioning

confidence: 99%

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Teipel

Ewers

Wolf

et al. 2010

Psychiatry Research: Neuroimaging

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MRI based volumetry of the hippocampus and amygdala has been suggested as a biomarker of Alzheimer's disease (AD). For validation of the candidate marker, however, effects of multicentre acquisition on measurement variability have to be considered. In the present study we determined effects of multicentre acqusitions of MRI data across 12 clinical sites within the German Competence Network on Dementias in 113 patients with clinically probable AD and 150 patients with amnestic mild cognitive impairment (MCI). Hippocampus and amygdala volumes were significantly reduced in AD compared to MCI patients using data pooled across centres. The between-centre effect accounted for 5 to 15% of within-centre variability. Using mixed effects regression, we found specific correlations between delayed recall of verbal and non-verbal material and global cognitive measures with hippocampus and amygdala volumes. In contrast drawing performance was not correlated with volume measures. ApoE4 genotype had no effect on volumetric measures. Power analysis for the detection of a difference in the volumes between AD and MCI patients across centres showed that multicentre variability did not significantly affect effect sizes. The total sample size needed is N= 58 for hippocampus and N= 158 for amygdala volumes. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for diagnostic trials and replicates essential findings from smaller scale monocentre studies.3

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“…In HD, it is the medium-spiny neurons (MSNs) in the striatum that undergo atrophy in early stages of the disease, while in AD, large pyramidal neurons in the CA1 zone of the hippocampus as well as neurons in the basal forebrain and the entorhinal cortex are sites of early disease [10][11][12] . The process of neuronal dysfunction and death is progressive, and early changes are followed by a more wide-spread atrophy of the brain 10,13 .…”

Section: Introductionmentioning

confidence: 99%

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Ehrnhoefer

Wong

Hayden

2011

Nat Rev Drug Discov

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Neurodegenerative diseases exemplified by Alzheimer's and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a 'model' for Alzheimer's disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways.

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Neuron Number in the Entorhinal Cortex and CA1 in Preclinical Alzheimer Disease

Abstract: There is little or no neuronal loss in aging or preclinical AD but substantial loss in very mild AD. The findings indicate that AD results in clinical deficits only when it produces significant neuronal loss.

Cited by 518 publications

References 46 publications

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

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