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Novel 'inflammatory plaque' pathology in presenilin-1 Alzheimer's disease

journal contribution
posted on 2023-05-17, 02:33 authored by Shepherd, C, Gregory, G, James VickersJames Vickers, Halliday, G
Inflammation, in the form of reactive astrocytes and microglia, is thought to play an important role in Alzheimer's disease (AD) pathogenesis where it correlates with brain atrophy and disease severity. The Aβ protein, which comprises senile plaques, is thought to be responsible for initiating this inflammatory response. Despite having a more aggressive disease process and greater Aβ deposition, few studies have investigated inflammation in early onset AD cases with mutations in the presenilin-1 (PS-1) gene. In fact, many researchers place importance on a variant plaque pathology in PS-1 cases, known as cotton wool plaques, which lack significant inflammatory infiltrate. We investigated the association between inflammation and plaque pathology in PS-1 AD. Classic cored, cotton wool and diffuse Aβ plaques were observed in all cases. PS-1 cases also exhibited a novel plaque pathology with a significantly greater inflammatory response in the form of reactive microglia and astrocytes. These 'inflammatory plaques' consisted of a dense cresyl violet-, silver-, and thioflavin S-positive, but Aβ-, tau-, apolipoprotein E (ApoE)-, non-Aβ component of Alzheimer's disease amyloid (NAC)- and PS-1-negative core. These findings indicate potent stimulator(s) of inflammation that are not typical of the Aβ that accumulates in the pathological hallmarks of sporadic AD. Identification of this substance may be important for the development of future therapeutic strategies.

History

Publication title

Neuropathology and Applied Neurobiology

Volume

31

Issue

5

Pagination

503-511

ISSN

0305-1846

Department/School

Menzies Institute for Medical Research

Publisher

Blackwell Publishing Ltd

Place of publication

9600 Garsington Rd, Oxford, England, Oxon, Ox4 2Dg

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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