In majority cases of age-dependent Alzheimer’s and Parkinson’s disease that
appear sporadic in the advanced age, the protein aggregates in the brain are
primarily composed of wild type misfolded disease proteins (again, characteristic
for each disease). Consequently, proteomics and genomics play an important role in
the discovery of genetic and other cellular factors that influence protein aggregation
and toxicity of these aggregated particles in the brain tissue, as well as in providing
important information for further therapeutic strategies. Some small model organ-
isms like baker’s yeast, nematode worm, and the fruit flyDrosophila melanogaster
are used for the investigation of pathologic processes caused by these diseases.
High-throughput genetic and proteomic screens of these model organisms have
enabled identification of genes that are involved in protein aggregation and
toxicity.^138
High-throughput genomic and proteomic tests can be used for the early detection
of neurodegenerative diseases and also for their fast and early discrimination and
differential diagnosis. Fundamental studies of the changes in cellular structures as a
consequence of neurodegenerative diseases were performed on tissue biopsies.^139
Newly, the changes in disease-affected human embryonic cells as model systems
were also investigated.^140 For non-(or less-) invasive studies, human blood serum
and cerebrospinal fluid are used as specimens.^141 Because of lower sampling
invasiveness, serum (or blood plasma) sampling shall be preferred. As shown by
Goldknopf,^142 patients with AD, PD, and amyothropic lateral sclerosis can be
discriminated by the use of 2D electrophoresis. All genomic investigations show
disease-specific changes that will be shortly discussed below. Recent proteomic
investigation demonstrated that in all investigated neurodegenerative diseases,
namely Alzheimer’s, Huntington’s, Parkinson’s, and amyotropic lateral sclerosis,
the formation of protein aggregates containing mutated or misfolded proteins
(or both) in neurons leads to their functional impairment and finally cell death.^143
To great extent, these changes are detected in the mitochondria, and they play a
major role in their dysfunction and finally in cell degeneration and death.^144
In Alzheimer’s disease, recent large genomic study identified genom-wide
association with the apolipoprotein E, a human plasma protein with relatively
high abundance.^145 Following transcriptomic and proteomic studies should demon-
strate the consequence of this finding. Proteomic analyses of brain biopsies show
(^138) Goldknopf ( 2008 ), pp. 1–8.
(^139) Zhang et al. ( 2008 ), pp. 923–932.
(^140) Glauber et al. ( 2014 ), p. e0002.
(^141) Harold et al. ( 2009 ), pp. 1088–1093.
(^142) Goldknopf ( 2008 ), pp. 1–8.
(^143) Citron et al. ( 1997 ), pp. 67–72.
(^144) Rodolfo et al. ( 2010 ), pp. 519–542.
(^145) Harold et al. ( 2009 ), pp. 1088–1093.
The Role of Proteomics in Personalized Medicine 203