Dataset Information

UDPMs in AD+CVD - Brain ureido degenerative protein modifications are associated with neuroinflammation and proteinopathy in Alzheimer's disease with cerebrovascular disease

ABSTRACT: In this study we have profiled the temporal lobe proteome of AD+CVD subjects and age-matched controls. We have studied the occurrence of uDPMs in the particulate and soluble brain proteomes isolated and analyzed by ultracentrifugation-electrostatic repulsion hydrophilic interaction chromatography (UC-ERLIC).

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Dementia

SUBMITTER: Xavier Gallart Palau

LAB HEAD: Siu Kwan Sze

PROVIDER: PXD006233 | Pride | 2017-09-11

REPOSITORIES: Pride

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Brain ureido degenerative protein modifications are associated with neuroinflammation and proteinopathy in Alzheimer's disease with cerebrovascular disease.

Gallart-Palau Xavier X Serra Aida A Lee Benjamin Sian Teck BST Guo Xue X Sze Siu Kwan SK

Journal of neuroinflammation 20170902 1

<h4>Background</h4>Brain degenerative protein modifications (DPMs) are associated with the apparition and progression of dementia, and at the same time, Alzheimer's disease with cerebrovascular disease (AD + CVD) is the most prevalent form of dementia in the elder population. Thus, understanding the role(s) of brain DPMs in this dementia subtype may provide novel insight on the disease pathogenesis and may aid on the development of novel diagnostic and therapeutic tools. Two essential DPMs known ...[more]

PMID: 28865468

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Project description:ObjectiveTo measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (β-amyloid [Aβ] and tau), structural imaging correlates, and clinical disease progression over time.MethodsThe study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years).ResultsCSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in Aβ-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia.ConclusionsNeuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.

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