Abstract
Hallmarks of Alzheimer’s disease (AD), a progressive neurodegenerative disease causing dementia, include protein aggregates such as amyloid beta plaques and tau neurofibrillary tangles in a patient’s brain. Understanding the complete composition and structure of protein aggregates in AD can shed light on the as-yet unidentified underlying mechanisms of AD development and progression. Biochemical isolation of aggregates coupled with mass spectrometry (MS) provides a comprehensive proteomic analysis of aggregates in AD. Dissection of these AD-specific aggregate components, such as U1 small nuclear ribonucleoprotein complex (U1 snRNP), provides novel insights into the deregulation of RNA splicing in the disease. In this review, we summarize the methodologies of laser capture microdissection (LCM) and differential extraction to analyze the aggregated proteomes in AD samples, and discuss the derived novel insights that may contribute to AD pathogenesis.
Highlights
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the most common form of dementia, listed as the sixth leading cause of death [1,2]
This study demonstrates the feasibility of proteomic analysis of minute amounts of laser capture microdissection (LCM)-isolated AD samples (Figure 1)
It will be highly interesting to further study if these RNA binding proteins contribute to Protein aggregation is a hallmark of AD typically associated with Aβ and hyperphosphorylated tau, other proteins can self-aggregate or co-aggregate with amyloid plaques and neurofibrillary tangles (NFT)
Summary
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the most common form of dementia, listed as the sixth leading cause of death [1,2]. Biochemical dissection of AD brain tissue identified pathological hallmarks of amyloid-β (Aβ)-containing amyloid plaques, and neurofibrillary tangles (NFT) comprising hyperphosphorylated Tau in both familial and sporadic patients [15], Tau mutations were identified in other forms of dementia, collectively termed tauopathy [16]. These results lead to the proposed amyloid cascade and Tau hypotheses [16,17]. The antibody-based IHC method is a targeted approach for detecting known aggregated proteins in the plaques and NFT of brain tissue, but the exact composition of the aggregated structures could not be uncovered.
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