Biomedical Engineering Reference
In-Depth Information
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Figure 5.6
Cells growing on the biochip surface.
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(Reprinted by kind permission of Dr Paul Galvin, Tyndall National
Institute Cork City, Republic of Ireland.)
type of research is the detection of misfolded and aggregated protein variants
that contribute to many human diseases including Alzheimer's disease (AD),
Lewy body dementia (LBD), frontotemporal dementia and Parkinson's disease
(PD). The diagnosis of such diseases is very challenging.
Cerebral spinal fluid (CSF) levels of Ab, tau and phosphorylated tau are
promising biomarkers for diagnosing AD. There is increasing evidence to
indicate that various soluble, aggregated oligomeric forms of Ab, a-syn and tau
are the relevant toxic species in different neurodegenerative diseases, and
specific detection of different aggregate species in CSF may provide a more
refined and powerful tool to facilitate early and accurate diagnosis of a variety
of such medical conditions. Additionally, this type of detection approach may
lead to an understanding of the mechanisms involved in the onset and
progression of these diseases. Protein aggregation is a common thread behind
numerous neurodegenerative diseases including AD, PD, LBD, tauopathies
and synucleinopathies. Aggregation of Ab has been correlated with AD,
aggregation of a-syn with PD, LBD and other synucleinopathies, and aggre-
gation of tau with AD and various tauopathies.
While the presence of fibrillar aggregates of these different proteins has been
a classic diagnostic feature of the respective diseases, increasing evidence
suggests that soluble oligomeric forms of these proteins are the relevant toxic
species. During the polymerization process from monomeric to fibrillar form,
each of the protein species must pass through different oligomeric states,
suggesting that various oligomeric species may represent earlier biomarkers for
these diseases compared with the presence of fibrillar forms. A rapidly growing
body of evidence indicates that oligomeric forms of Ab are key factors in the
onset and progression of AD. Ab forms a number of soluble intermediate or
metastable structures which may contribute to toxicity. Cortical levels of
soluble Ab correlate well with the cognitive impairment and loss of synaptic
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