The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease

Delacourte, André; David, Jean‐Philippe; Sergeant, Nicolas; Buée, Luc; Wattez, A.; Vermersch, Patrick; Ghozali, Farida; Fallet-Bianco, Catherine; Pasquier, Florence; Lebert, Florence; Petit, H; Menza, C. Di

doi:10.1212/wnl.52.6.1158

Cited by 741 publications

(544 citation statements)

References 40 publications

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“…The spreading of NFT pathology in AD follows a relatively stereotyped sequence with limbic and neocortical associative areas being heavily affected at advanced stages, but with sparing of several brain regions (e.g., cerebellum, spinal cord) [5,6]. The detection of PHF-tau proteins in cortical areas in AD patients by biochemical methods follows a sequence comparable to that observed in neuropathological studies [7]. In other neurodegenerative diseases characterized by the presence of abnormal tau-positive fibrillary inclusions (tauopathies), the distribution of these cellular inclusions follows a different neuroanatomical pattern.…”

Section: Introductionsupporting

confidence: 55%

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

et al. 2004

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In Alzheimer's disease (AD), selective expression of tau isoforms might underlie the susceptibility of different brain areas to develop neurofibrillary tangles and this pattern might change in the disease. In this study, we have analyzed in control subjects and in sporadic AD patients the pattern of expression of tau mRNA and tau proteins in areas unaffected (cerebellar cortex, white matter), moderately affected (occipital striate cortex, thalamus, caudate nucleus, and putamen) or strongly affected by neurofibrillary tangles (temporal and frontal associative cortex). After RT-PCR amplification, five products corresponding to the tau mRNAs containing exons 2 and 3, exon 2, without exons 2 or 3, with exon 10 and without exon 10 were identified. In control subjects, these five PCR products were present in all areas except in white matter, where transcripts with exons 2 or exons 2 and 3 were not identified. In AD patients, the same pattern of transcripts was observed in different areas, regardless of the presence of neurofibrillary lesions. After dephosphorylation of soluble tau proteins, the six tau isoforms were identified in the same areas by immunoblotting, including in the white matter, suggesting that most tau isoforms with exons 2 and 3 are transported along axons. The relative expression of 0N3R isoforms was higher in the temporal cortex than in the cerebellar cortex, both in control and AD subjects. The qualitative pattern of expression was identical in subjects with or without an APOE4 allele. Our results suggest that splicing regulation of the tau gene and the relative expression of tau isoforms are not significantly changed in sporadic cases of the disease, although differential expression of tau isoforms in temporal cortex might underlie this brain area susceptibility to neurofibrillary tangles formation.

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Section: Introductionsupporting

confidence: 55%

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

et al. 2004

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“…Although controversy exists over whether it is neurofibrillary tangles, amyloid deposits, or neuronal and synaptic loss that constitute the primary neuropathologic process that underlies the disease, neurofibrillary tangle densities in the medial temporal lobes do correlate with clinical evidence of memory impairment (Giannakopoulos et al, 2003). Delacourte et al (1999) conducted a detailed postmortem analysis of neurofibrillary degeneration in the brains of 130 patients of different ages and differing degrees of dementia (ranging from nondemented to severe AD). On the basis of their findings, they proposed that neurofibrillary degeneration progresses through a 10-stage process, beginning in the entorhinal cortex and then proceeding to affect the hippocampus, the anterior temporal cortex, the inferior temporal cortex, and the middle temporal cortex.…”

Section: Discussionmentioning

confidence: 99%

Progressive impairment on neuropsychological tasks in a longitudinal study of preclinical Alzheimer's disease.

et al. 2007

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Previous research suggests that patients with Alzheimer's disease exhibit cognitive impairment in the years preceding a clinical diagnosis. Memory impairments are particularly pronounced, but the relative degree to which other cognitive functions are impaired and the speed with which they decline during the preclinical years remains unclear. The authors report a detailed neuropsychological evaluation of 11 patients over the course of 3 years up to and including the 1st year of nonnormal diagnosis. The results suggest that performance falls off rapidly in all areas of cognitive functioning but that abilities thought to be subserved by the medial and lateral temporal lobes (episodic and semantic memory, respectively) appear to be substantially more impaired than those abilities thought to be subserved by the frontal lobes.

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“…In contrast, subjects with stages V and VI meet the neuropathological criteria for the diagnosis of AD and are severely demented. The Braak staging system which is exclusively based on morphological findings has recently been nicely confirmed by a biochemical pathway of tau pathology in aging and AD (8,9).…”

Section: Alzheimer's Diseasementioning

confidence: 95%

The Neuropathological Spectrum of Neurodegenerative Tauopathies

Tolnay

Probst

2003

IUBMB Life

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SummaryAbundant neurofibrillary lesions made of abnormal and hyperphosphorylated microtubule-associated protein tau constitute one of the defining neuropathological features of Alzheimer's disease. However, tau containing filamentous deposits in neurons and/or glial cells also define a heterogeneous group of neurodegenerative disorders clinically characterized by dementia and/or motor syndromes. Thus, all these disorders are collectively grouped under the generic term of tauopathies. In the present review we outline the morphological and biochemical characteristics of some major tauopathies, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease. The second part will deal with the recent discovery of tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 which demonstrates that tau dysfunction can lead to neurodegeneration. Finally, we will discuss the very recent finding of 'tau-deficient' tauopathy in a subset of frontotemporal dementia cases. IUBMB Life, 55: 299-305, 2003

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The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease

Abstract: The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.

Cited by 741 publications

References 40 publications

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's disease

Progressive impairment on neuropsychological tasks in a longitudinal study of preclinical Alzheimer's disease.

The Neuropathological Spectrum of Neurodegenerative Tauopathies

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