Clinical Correlates of Cortical and Nucleus Basalis Pathology in Alzheimer Dementia

Samuel, William; Terry, Robert D.; DeTeresa, Richard; Butters, Nelson; Masliah, Eliezer

doi:10.1001/archneur.1994.00540200048015

Cited by 136 publications

(52 citation statements)

References 39 publications

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“…In addition to cell death of basal forebrain neurons, neuropathology also develops in the basal forebrain with Alzheimer's disease. Neuropathology in the basal forebrain seems to be highly correlated with scores on tests for memory ability, whereas loss of cortical synapses was strongly correlated with scores on tests for cognitive ability (Samuel et al, 1994). Neuropathology in the cholinergic basal forebrain precedes cortical volume loss and cholinergic cell loss, suggesting that changes to cholinergic neurons are a primary event (Cullen et al, 1997).…”

Section: Memory Storage and Agingmentioning

confidence: 98%

A structural basis for memory storage in mammals

Woolf

1998

Progress in Neurobiology

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AbstractÐIt is proposed that altered dendrite length and de novo formation of new dendrite branches in cholinoceptive cells are responsible for long-term memory storage, a process enabled by the degradation of microtubule-associated protein-2. These memories are encoded as modality-speci®c associable representations. Accordingly, associable representations are con®ned to cytoarchitectonic modules of the cerebral cortex, hippocampus, and amygdala. The proposed sequence of events leading to long-term storage in cholinoceptive dendrites begins with changes in neuronal activity, then in neurotrophin release, followed by enhanced acetylcholine release, muscarinic response, calcium in¯ux, degradation of microtubule-associated protein-2, and ®nally new dendrite structure. Hypothetically, each associable representation consists of altered dendrite segments from approximately 5000±15 000 cholinoceptive cells contained within one or a few module(s). Simultaneous restructuring during consolidation of long-term memory is hypothesized to result in a similar infrastructure among dendrite sets, facilitating co-activation of those dendrite sets by neurotransmitters such as acetylcholine, and conceivably enabling high energy interactions between those dendrites by phenomena such as quantum optical coherence. Based on the speci®c architecture proposed, it is estimated that the human telencephalon contains enough dendrites to encode 50 million associable representations in a lifetime, or put another way, to encode one new associable representation each minute. The implications that this proposal has regarding treatments for Alzheimer's disease are also discussed. #

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Section: Memory Storage and Agingmentioning

confidence: 98%

A structural basis for memory storage in mammals

Woolf

1998

Progress in Neurobiology

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“…Although senile plaques and neurofibrillary tangles (NFTs) in the brain are considered the pathological hallmarks, the presences of these hallmarks seem not correlated to the severity of dementia (Arriagada, et al, 1992, Samuel, et al, 1994, Gomez-Isla, et al, 1997. In contrast, neuronal loss in certain selected brain regions represents a direct pathological cause for dementia (Bondareff, et al, 1982, Whitehouse, et al, 1982, Samuel, et al, 1994, Gomez-Isla, et al, 1997, Bussiere, et al, 2003. Furthermore, the hippocampus is one of the most vulnerable brain regions to AD, and the degeneration in this brain structure may directly underlie memory deficit, the earliest symptom of AD (Barber, et al, 2001, Thompson, et al, 2004.…”

Section: Introductionmentioning

confidence: 99%

Adult neurogenesis is functionally associated with AD-like neurodegeneration

Chen

Nakajima

Choi

et al. 2008

Neurobiology of Disease

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Alzheimer's disease (AD) is predominantly characterized by progressive neuronal loss in the brain. It has been recently found that adult neurogenesis in the hippocampal dentate gyrus of AD patients is significantly enhanced, while its functional significance is still unknown. By using an AD-like neurodegeneration mouse model, we show here that neurogenesis in the dentate gyrus was neurodegenerative stage-dependent. At early stages of neurodegeneration, neurogenesis was significantly enhanced and newly generated neurons migrated into the local neuronal network. Up to late stages of neurodegeneration, however, the survival of newly generated neurons was impaired so that the enhanced neurogenesis could not be detected any more. Most interestingly, these dynamic changes in neurogenesis were correlated with the severity of neuronal loss in the dentate gyrus, indicating that neurogenesis may work as a self-repairing mechanism to compensate for neurodegeneration. Therefore, to enhance endogenous neurogenesis at early stages of neurodegeneration may be a valuable strategy to delay neurodegenerative progress.

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“…Some authors suggest that the accumulation and deposition of A␤ peptides and the subsequent formation of senile plaques are the primary cause of neurodegeneration and behavioral changes in AD patients (Kisilevsky and Fraser, 1997;Selkoe, 2001;Hardy and Selkoe, 2002). Several studies, however, have indicated that A␤ plaque burden does not correlate with dementia in patients (Arriagada et al, 1992;Samuel et al, 1994;McLean et al, 1999), and investigations using murine AD models have so far been unable to provide a clear answer to this question. Therefore, although nobiletin reduces A␤ plaque pathology and improves cognitive deficits in a transgenic mouse model of AD, it is not determined whether a reduction in A␤ production or deposition is responsible for the improvement of cognitive deficits by nobiletin.…”

mentioning

confidence: 99%

Nobiletin, a Citrus Flavonoid, Improves Memory Impairment and Aβ Pathology in a Transgenic Mouse Model of Alzheimer's Disease

Onozuka

Nakajima²,

Matsuzaki³

et al. 2008

J Pharmacol Exp Ther

205

122

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Increasing evidence suggests that the elevation of ␤-amyloid (A␤) peptides in the brain is central to the pathogenesis of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, enhances cAMP/protein kinase A/extracellular signalregulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons and ameliorates A␤-induced memory impairment in AD model rats. For the first time, we report that this natural compound improves memory deficits in amyloid precursor protein (APP) transgenic mice that overexpress human APP695 harboring the double Swedish and London mutations [APP-SL 7-5 transgenic (Tg) mice]. Our enzyme-linked immunosorbent assay (ELISA) also showed that administration of nobiletin to the transgenic mice for 4 months markedly reduced quantity of guanidine-soluble A␤ 1-40 and A␤ 1-42 in the brain. Furthermore, consistent with the results of ELISA, by immunohistochemistry with anti-A␤ antibody, it was evidently shown that the administration of nobiletin decreased the A␤ burden and plaques in the hippocampus of APP-SL 7-5 Tg mice. These findings suggest that this natural compound has potential to become a novel drug for fundamental treatment of AD.

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Clinical Correlates of Cortical and Nucleus Basalis Pathology in Alzheimer Dementia

Cited by 136 publications

References 39 publications

A structural basis for memory storage in mammals

A structural basis for memory storage in mammals

Adult neurogenesis is functionally associated with AD-like neurodegeneration

Nobiletin, a Citrus Flavonoid, Improves Memory Impairment and Aβ Pathology in a Transgenic Mouse Model of Alzheimer's Disease

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