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Review
. 2018 Nov 12;6(4):46.
doi: 10.3390/proteomes6040046.

Deep Profiling of the Aggregated Proteome in Alzheimer's Disease: From Pathology to Disease Mechanisms

Brianna M Lutz  1 , Junmin Peng  2
Affiliations
Review

Deep Profiling of the Aggregated Proteome in Alzheimer's Disease: From Pathology to Disease Mechanisms

Brianna M Lutz et al. Proteomes. .

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.

Keywords: Alzheimer’s disease; U1 snRNP; laser capture microdissection; mass spectrometry; protein aggregation; proteome; proteomics; splicing.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Methods for profiling the aggregated proteome in Alzheimer’s Disease (AD). Isolation of protein aggregates in AD brain can be accomplished using laser capture microdissection or differential extraction. Laser capture microdissection specifically captures protein aggregates, resulting in a protein yield of around 2 µg for 1000 plaques. Using this minute amount, less than 1000 proteins were identified using LC-MS/MS. Differential extraction, the process of isolating insoluble aggregates through repeated centrifugation in varying reagents, yields around 100 µg of protein and around 5000 proteins identified using LC-MS/MS. Regardless of the method of aggregate isolation, protein targets need to be validated using specific immunohistochemical techniques and their function can be determined using comparable research models.
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References

    1. James B.D., Leurgans S.E., Hebert L.E., Scherr P.A., Yaffe K., Bennett D.A. Contribution of alzheimer disease to mortality in the united states. Neurology. 2014;82:1045–1050. doi: 10.1212/WNL.0000000000000240. - DOI - PMC - PubMed
    1. Scheltens P., Blennow K., Breteler M.M., de Strooper B., Frisoni G.B., Salloway S., Van der Flier W.M. Alzheimer’s disease. Lancet. 2016;388:505–517. doi: 10.1016/S0140-6736(15)01124-1. - DOI - PubMed
    1. Wimo A., Guerchet M., Ali G.C., Wu Y.T., Prina A.M., Winblad B., Jönsson L., Liu Z., Prince M. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement. 2017;13:1–7. doi: 10.1016/j.jalz.2016.07.150. - DOI - PMC - PubMed
    1. Graham W.V., Bonito-Oliva A., Sakmar T.P. Update on alzheimer’s disease therapy and prevention strategies. Annu. Rev. Med. 2017;68:413–430. doi: 10.1146/annurev-med-042915-103753. - DOI - PubMed
    1. Tanzi R.E. The genetics of alzheimer disease. Cold Spring Harb. Perspect. Med. 2012;2 doi: 10.1101/cshperspect.a006296. - DOI - PMC - PubMed

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