Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology

Schönheit, B; Zarski, Rosemarie; Ohm, Thomas G.

doi:10.1016/j.neurobiolaging.2003.09.009

Cited by 225 publications

(152 citation statements)

References 38 publications

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“…In this situation, axonal leakage may be at an early and reversible stage. This also suggests that NFTs originate earlier than SPs [5,11,38,39] .…”

Section: Discussionmentioning

confidence: 99%

“…For example, the leakage of overproduced intra-axonal Aβ or extra-axonal proteolysis of the leaked amyloid precursor protein may result in Aβ plaques [33] , which may explain the Aβ plaques observed in brain areas with unimpaired neural functions [2,11] . Axonal leakage may be present at axon terminals of affected neurons located far from their termination areas, however, these areas may still exhibit unimpaired function if their neurons are not affected despite the presence of plaques.…”

Section: Discussionmentioning

confidence: 99%

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The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

Xiao

Wang

et al. 2011

Neurosci. Bull.

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Objective The production of neurotoxic β-amyloid and the formation of hyperphosphorylated tau are thought to be critical steps contributing to the neuropathological mechanisms in Alzheimer's disease (AD). However, there remains an argument as to their importance in the onset of AD. Recent studies have shown that axonopathy is considered as an early stage of AD. However, the exact relationship between axonopathy and the origin and development of classic neuropathological changes such as senile plaques (SPs) and neurofi brillary tangles (NFTs) is unclear. The present study aimed to investigate this relationship. Methods Postmortem tracing, combined with the immunohistochemical or immunofl uorescence staining, was used to detect axonopathy and the formation of SPs and NFTs. Results "Axonal leakage"-a novel type of axonopathy, was usually accompanied with the extensive swollen axons and varicosities, and was associated with the origin and development of Aβ plaques and hyperphosphorylated tau in the brains of AD patients. Conclusion Axonopathy, particularly axonal leakage, might be a key event in the initiation of the neuropathological processes in AD.

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“…In this situation, axonal leakage may be at an early and reversible stage. This also suggests that NFTs originate earlier than SPs [5,11,38,39] .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

Xiao

Wang

et al. 2011

Neurosci. Bull.

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“…34 Interestingly, despite compelling evidence that Aβ is upstream of tau in AD pathogenesis, 5,9,11,39,45-52 abnormal, pre-NFT tau is usually detectable before plaques. 55,56 This may symbolize that soluble, oligomeric Aβ, rather than plaques, provoke tau pathology, and that the pattern of plaque spreading simply reflects net rates of insoluble Aβ accumulation within various regions of brain over time.…”

Section: Aβ and Tau Spread Stereotypically Through The Brainmentioning

confidence: 99%

Alzheimer disease

Nussbaum

Seward

Bloom

2013

Prion

109

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“…From the entorhinal cortex, NFTs spread first to the CA1 (cornu ammonis 1) and subiculum, then to the CA2/3 and finally to the CA4 hippocampal subfield. 15 Newer techniques (discussed under Brain mapping as a tool to study neurodegeneration, the next section) can now better localize discrete subregional changes that can predict disease progression in MCI. Subregion-specific changes between AD and MCI can also be related to known cytoarchitectural subdivisions.…”

Section: Figmentioning

confidence: 99%

“…64 Neuropathological studies describe hippocampal NFT pathology as a stage-like process affecting the subiculum and CA1 subfields first, followed by the CA2/3 and finally the CA4 subfields. 15 In 2004, Thompson et al 59 applied a hippocampal radial atrophy mapping technique to AD and normal elderly subjects, which revealed profound differences between the two groups. Using the same technique, Frisoni et al 65 demonstrated that the CA1 area and parts of the subiculum show 15-20% atrophy in AD relative to normal controls.…”

Section: Brain Mapping In Neurodegenerative Dementiasmentioning

confidence: 99%

Brain Mapping as a Tool to Study Neurodegeneration

Apostolova

Thompson

2007

Neurotherapeutics

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Summary: Alzheimer's disease (AD) is the most common neurodegenerative disorder for those 65 years or older; it currently affects 4.5 million in the United States and is predicted to rise to 13.2 million by the year 2050. Neuroimaging and brain mapping techniques offer extraordinary power to understand AD, providing spatially detailed information on the extent and trajectory of the disease as it spreads in the living brain. Computational anatomy techniques, applied to large databases of brain MRI scans, reveal the dynamic sequence of cortical and hippocampal changes with disease progression and how these relate to cognitive decline and future clinical outcomes. People who are mildly cognitively impaired, in particular, are at a fivefold increased risk of imminent conversion to dementia, and they show specific structural brain changes that are predictive of imminent disease onset. We review the principles and key findings of several new methods for assessing brain degeneration, including voxel-based morphometry, tensor-based morphometry, cortical thickness mapping, hippocampal atrophy mapping, and automated methods for mapping ventricular anatomy. Applications to AD and other dementias are discussed, with a brief review of related findings in other neurological and neuropsychiatric illnesses, including epilepsy, HIV/AIDS, schizophrenia, and disorders of brain development.

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Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology

Cited by 225 publications

References 38 publications

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease

Alzheimer disease

Brain Mapping as a Tool to Study Neurodegeneration

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