Z Abdi, K X Yong, J M Schott, A Gatt, T Revesz, S J Crutch, T Lashley
{"title":"Pathological Characterisation of Posterior Cortical Atrophy in Comparison With Amnestic Alzheimer's Disease.","authors":"Z Abdi, K X Yong, J M Schott, A Gatt, T Revesz, S J Crutch, T Lashley","doi":"10.1111/nan.70007","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Posterior cortical atrophy (PCA) is a predominantly young-onset neurodegenerative syndrome, typically caused by Alzheimer's disease (PCA-AD). PCA-AD presents with visual and spatial dysfunction attributed to occipito-parietal or 'posterior' brain regions rather than memory difficulties characteristic of typical amnestic-led Alzheimer's disease (a-AD) attributed to medial temporal regions. Imaging and neuropathological studies suggest that PCA-AD is associated with a more posterior distribution of tau neurofibrillary tangles (NFTs), whereas β-amyloid pathology (Aβ) is diffusely deposited throughout the cortex. This study characterised the neuropathological substrates of PCA-AD in comparison with a-AD, to further understanding of the biological basis of phenotypical heterogeneity in AD.</p><p><strong>Methods: </strong>Immunohistochemistry for Aβ; tau; the microglial markers CD68, CR3-43 and Iba1; α-synuclein; and TDP-43 was carried out on 26 PCA-AD and 27 age and gender-matched a-AD cases at the Queen Square Brain Bank. Aβ, tau and the three microglial markers were quantified in the superior frontal, superior temporal, superior parietal and occipital (primary visual cortex) cortices, with α-synuclein and TDP-43 assessed using formal staging criteria. In addition, microglial circularity, a morphological indicator of microglial activation state, was calculated.</p><p><strong>Results: </strong>There was a higher load of Aβ and tau in the parietal region of PCA-AD compared to a-AD. In the PCA-AD compared to the a-AD group, there were significant increases in tau load in parietal and frontal relative to temporal regions. There was no difference in cerebral amyloid angiopathy (CAA) severity between PCA-AD and a-AD. There was a significantly lower temporal CD68 load in a-AD compared with PCA-AD. In a-AD, CD68 load was lowest and tau load highest in the temporal relative to all other regions.</p><p><strong>Conclusions: </strong>This study demonstrates differences in the distribution of Aβ and tau and variations in regional neuroinflammatory response in PCA-AD and a-AD. These findings extend our understanding of the biological substrates underpinning PCA-AD and highlight the potential for exploring phenotypic variants to understand selective vulnerability in neurodegenerative diseases.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"51 2","pages":"e70007"},"PeriodicalIF":4.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964714/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology and Applied Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/nan.70007","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: Posterior cortical atrophy (PCA) is a predominantly young-onset neurodegenerative syndrome, typically caused by Alzheimer's disease (PCA-AD). PCA-AD presents with visual and spatial dysfunction attributed to occipito-parietal or 'posterior' brain regions rather than memory difficulties characteristic of typical amnestic-led Alzheimer's disease (a-AD) attributed to medial temporal regions. Imaging and neuropathological studies suggest that PCA-AD is associated with a more posterior distribution of tau neurofibrillary tangles (NFTs), whereas β-amyloid pathology (Aβ) is diffusely deposited throughout the cortex. This study characterised the neuropathological substrates of PCA-AD in comparison with a-AD, to further understanding of the biological basis of phenotypical heterogeneity in AD.
Methods: Immunohistochemistry for Aβ; tau; the microglial markers CD68, CR3-43 and Iba1; α-synuclein; and TDP-43 was carried out on 26 PCA-AD and 27 age and gender-matched a-AD cases at the Queen Square Brain Bank. Aβ, tau and the three microglial markers were quantified in the superior frontal, superior temporal, superior parietal and occipital (primary visual cortex) cortices, with α-synuclein and TDP-43 assessed using formal staging criteria. In addition, microglial circularity, a morphological indicator of microglial activation state, was calculated.
Results: There was a higher load of Aβ and tau in the parietal region of PCA-AD compared to a-AD. In the PCA-AD compared to the a-AD group, there were significant increases in tau load in parietal and frontal relative to temporal regions. There was no difference in cerebral amyloid angiopathy (CAA) severity between PCA-AD and a-AD. There was a significantly lower temporal CD68 load in a-AD compared with PCA-AD. In a-AD, CD68 load was lowest and tau load highest in the temporal relative to all other regions.
Conclusions: This study demonstrates differences in the distribution of Aβ and tau and variations in regional neuroinflammatory response in PCA-AD and a-AD. These findings extend our understanding of the biological substrates underpinning PCA-AD and highlight the potential for exploring phenotypic variants to understand selective vulnerability in neurodegenerative diseases.
期刊介绍:
Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.