Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease

West, Mark J.; Coleman, Paul D.; Flood, Dorothy G.; Troncoso, J. C.

doi:10.1016/s0140-6736(94)92338-8

Cited by 1,151 publications

(798 citation statements)

References 28 publications

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“…However, in the CA1 region, hTau‐A152T (L1) mice had a string‐like pattern of HT7 immunostaining that was not seen in hTau‐WT (L32) mice (Figs 3D–I and EV3D–M), possibly indicating a difference in the subcellular localization of hTau‐A152T versus hTau‐WT in CA1 pyramidal cells, which are particularly vulnerable to AD 33.…”

Section: Resultsmentioning

confidence: 95%

Expression of A152T human tau causes age‐dependent neuronal dysfunction and loss in transgenic mice

et al. 2016

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A152T‐variant human tau (hTau‐A152T) increases risk for tauopathies, including Alzheimer's disease. Comparing mice with regulatable expression of hTau‐A152T or wild‐type hTau (hTau‐WT), we find age‐dependent neuronal loss, cognitive impairments, and spontaneous nonconvulsive epileptiform activity primarily in hTau‐A152T mice. However, overexpression of either hTau species enhances neuronal responses to electrical stimulation of synaptic inputs and to an epileptogenic chemical. hTau‐A152T mice have higher hTau protein/mRNA ratios in brain, suggesting that A152T increases production or decreases clearance of hTau protein. Despite their functional abnormalities, aging hTau‐A152T mice show no evidence for accumulation of insoluble tau aggregates, suggesting that their dysfunctions are caused by soluble tau. In human amyloid precursor protein (hAPP) transgenic mice, co‐expression of hTau‐A152T enhances risk of early death and epileptic activity, suggesting copathogenic interactions between hTau‐A152T and amyloid‐β peptides or other hAPP metabolites. Thus, the A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors.

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Section: Resultsmentioning

confidence: 95%

Expression of A152T human tau causes age‐dependent neuronal dysfunction and loss in transgenic mice

et al. 2016

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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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“…Cerebral cortex [15,16] and hippocampus [17] were thought to be particularly affected, but also cerebellar Purkinje cells [18]. More recent studies employing stereologically-based sampling [19][20][21][22] to derive estimates of neuronal numbers in three-dimensional space have arrived at more conservative conclusions, that neuron loss with ageing is either undetectable or relatively mild [23,24]. Estimating the magnitude of neuronal loss in humans is complicated by the fact that most elderly brains from subjects over the age of 80 years are affected by the pathological changes of amyloid plaque and neurofibrillary tangle formation, the two hallmarks, when present in substantial numbers, of AD.…”

Section: Microscopic Brain Changes With Agementioning

confidence: 99%

Ageing and the brain

2007

The Journal of Pathology

177

111

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In this review, the evidence for changes in the human brain with ageing at both the macroscopic and microscopic levels is summarized. Loss of neurons is now recognized to be more modest than initial studies suggested and only affects some neuron populations. Accompanying loss of neurons is some reduction in the size of remaining neurons. This reflects a reduced size of dendritic and axonal arborizations. Some of the likely causes of these changes, including free radical damage resulting from a high rate of oxidative metabolism in neurons, glycation and dysregulation of intracellular calcium homeostasis, are discussed. The roles of genes and environmental factors in causing and responding to ageing changes are explored.

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Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease

Cited by 1,151 publications

References 28 publications

Expression of A152T human tau causes age‐dependent neuronal dysfunction and loss in transgenic mice

Expression of A152T human tau causes age‐dependent neuronal dysfunction and loss in transgenic mice

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

Ageing and the brain

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