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

By M. West, P. Coleman, D. Flood, J. Troncoso. 1994

The distinction between the neurodegenerative changes that accompany normal ageing and those that characterise Alzheimer's disease is not clear. The resolution of this issue has important implications for the design of therapeutic and investigative strategies. To this end we have used modern stereological techniques to compare the regional pattern of neuronal cell loss in the hippocampus related to normal ageing to that associated with Alzheimer's disease. The loss related to normal ageing was evaluated from estimates of the total number of neurons in each of the major hippocampal subdivisions of 45 normal ageing subjects who ranged in age from 13 to 101 years. The Alzheimer's disease related losses were evaluated from similar data obtained from 7 cases of Alzheimer's disease and 14 age matched controls. Qualitative differences were observed in the regional patterns of neuronal loss related to normal ageing and Alzheimer's disease. The most distinctive Alzheimer's disease related neuron loss was seen in the CA1 region of the hippocampus. In the normal ageing group there was almost no neuron loss in this region (final neuron count in the CA1 region: 4.40 x 10(6) neurons for the Alzheimer's disease group vs 14.08 x 10(6) neurons in the normal ageing group). It is concluded that the neurodegenerative processes associated with normal ageing and with Alzheimer's disease are qualitatively different and that Alzheimer's disease is not accelerated by ageing but is a distinct pathological process.

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Citations in the corpus

Human Hippocampal Neurogenesis Persists throughout Aging (2018, positive): “Using histological techniques that could not distinguish mature and immature neurons, several groups estimated that DG neurons did not decline in aging humans (Harding et al., 1998; Simi c et al., 1997; West et al., 1994).”
A pathophysiological framework of hippocampal dysfunction in ageing and disease (2011, background): “, that CA1 and the subiculum are also heavily involved, and that the dentate gyrus and CA3 are relatively preserve”
Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation (1996, background): “Degenerative changes include neuronal cell loss in the hilus and CA regions (Landfield et al., 1981; Flood and Coleman, 1988; West et al., 1994 ) reduced synaptic density (Bondareff and Geinisman, 1976), reduced postlesion sprouting (McWilliams and Lynch, 1984) and decreased glucose utilization (Ga”
Automated segmentation of hippocampal subfields from ultra‐high resolution in vivo MRI (2009, background): “The distinct subregions composing the hippocampus have been implicated in different memory subsystems (Gabrieli et al., 1997; Zeineh et al., 2003), and shown to be differentially affected in normal aging and AD (West et al., 1994; Fukutani et al., 1995; Small et al., 1999; Small et al., 2000).”
Pathways towards and away from Alzheimer's disease (2004, background): “A neuron's demise Loss of neurons in the entorhinal cortex, hippocampus, frontal, parietal and temporal cortices of AD patients has been documente”
Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. (2004, background): “[255] West MJ, Coleman PD, Flood DG, Troncoso JC.”
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice (2011, methodology): “We chose this site for the injection according to previous studies that described large number of NFTs and extensive neuron loss from the CA1 region of the hippocampus in patients with AD in comparison with age-matched controls [32-35].”
Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease (1997, methodology): “In the AD group, we have six cases with a larger number of CA1 neurons than were reported by West et al. (1994).”
Murine Features of Neurogenesis in the Human Hippocampus across the Lifespan from 0 to 100 Years (2010, background): “Stereological studies of the human DG, covering samples up to 101 years of age, determined that the number of granule cells in humans is very stable across the lifespan but varies greatly [70,71].”
Primary age-related tauopathy (PART): a common pathology associated with human aging (2014, background): “Most relevant prior studies have either focused on the most severe cases with TPSD or have investigated the associations between medial temporal lobe or brainstem tau pathology related to AD [5, 6, 11, 12, 19, 48, 49, 55, 56, 79, 133, 134, 144].”
The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications (2004, background): “For example, CA1, which is particularly susceptible in Alzheimer’s disease (West et al. 1994) and hypoxic brain injury (Petito et al.”
Classification and basic pathology of Alzheimer disease (2009, background): “Focally, severe neuronal loss has been documented in layer II of the entorhinal cortex where the loss may reach 90% of the normal neuronal population in the most advanced cases [130], in the CA1 sector (where the number of neurons was reduced threefold in Alzheimer cases) [344], in the superior temp”
Immune activation in brain aging and neurodegeneration: too much or too little? (2009, background): “…is the strongest risk factor for neurodegenerative diseases, and while aging is not considered a disease, it results in a significant increase in glial activation (see Figure 2), complement factors, inflammatory mediators, and brain atrophy (Lu et al., 2004; Streit et al., 2008; West et al., 1994).”
Neural mechanisms of ageing and cognitive decline (2010, background): “At the histopathological level, neuronal loss, beginning in the entorhinal cortex and the CA1 field of the hippocampus, together with volume loss in the medial temporal lobe, distinguishes normal ageing from the cognitive decline associated with Alzheimer's diseas”