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Title:
Neuropathologically defined subtypes of Alzheimerās disease differ significantly from neurofibrillary tangle-predominant dementia | Acta Neuropathologica
Description:
Alzheimerās disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (n = 18) with LP AD (n = 19), as well as the other AD subtypes, typical AD (n = 52) and HpSp AD (n = 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical β-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aβ immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70 %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.
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neuritic amyloid plaques basal ganglia neurofibrillary tangle-predominant dementia digital microscopy month download article/chapter cortical β-amyloid burden log-normal size distribution short-term clinical outcomes mapt h1 haplotype tangle-predominant dementia nacp/alpha-synuclein immunoreactivity tangle predominant form neuropathologically defined subtypes late-onset alzheimer disease neocortical neurofibrillary tangles diffuse neurofibrillary tangles neurofibrillary tangle type full article pdf privacy choices/manage cookies showed expected patterns limbic predominant alzheimer limbic-predominant ad early-onset alzheimer late-onset alzheimer senile plaques inhibits abeta deposition human subject research cortical amyloid neurofibrillary tangles mayo adrc grant fluorescent microscopy disease research program show hpsp ad distinct clinical characteristics european economic area female sex predominance progressive supranuclear palsy knopman ds sporadic 4-repeat tauopathy heat-stable microtubule monica castanedes-casey pathogenetic aspects distinct ļæ½mini-mental stateā conditions privacy policy frontotemporal lobar degeneration shorter disease duration argyrophilic grain disease mayo clinic study article log nft conformational epitope
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headline:Neuropathologically defined subtypes of Alzheimerās disease differ significantly from neurofibrillary tangle-predominant dementia
description:Alzheimerās disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (nĀ =Ā 18) with LP AD (nĀ =Ā 19), as well as the other AD subtypes, typical AD (nĀ =Ā 52) and HpSp AD (nĀ =Ā 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical β-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aβ immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70Ā %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.
datePublished:2012-09-12T00:00:00Z
dateModified:2012-09-12T00:00:00Z
pageStart:681
pageEnd:692
sameAs:https://doi.org/10.1007/s00401-012-1044-y
keywords:
Alzheimer disease
Neurofibrillary tangle-predominant dementia
APOE
Digital microscopy
MAPT
Neurofibrillary tangles
Amyloid plaques
Basal ganglia
Pathology
Neurosciences
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headline:Neuropathologically defined subtypes of Alzheimerās disease differ significantly from neurofibrillary tangle-predominant dementia
description:Alzheimerās disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (nĀ =Ā 18) with LP AD (nĀ =Ā 19), as well as the other AD subtypes, typical AD (nĀ =Ā 52) and HpSp AD (nĀ =Ā 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical β-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aβ immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70Ā %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.
datePublished:2012-09-12T00:00:00Z
dateModified:2012-09-12T00:00:00Z
pageStart:681
pageEnd:692
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keywords:
Alzheimer disease
Neurofibrillary tangle-predominant dementia
APOE
Digital microscopy
MAPT
Neurofibrillary tangles
Amyloid plaques
Basal ganglia
Pathology
Neurosciences
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