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December 06-07 , 2018
Amsterdam, Nether l ands
Journal of Neuropsychiatry
ISSN: 2471-8548
Alzheimer’s and Dementia 2018
1 3
t h
W o r l d c o n g r e s s o n
Alzheimer’s and Dementia
W
idespread phenotypic differences observed among Alzheimer’s
disease (AD) patients are one of the diverse clinical manifestations
in all neurodegenerative diseases. Deciphering the molecular mechanisms
that underpin such differences especially for an idiopathic disease is rather
challenging. Aggregation of amyloid-β (Aβ) peptides has long been known as
the key trigger in AD pathology. Polymorphism observed within the aggregation
end products of Aβ fibrils seem to correlate with clinically observed pathologic
variations, which has in part, corroborated the hypothesis that conformeric strains
of Aβ aggregates could manifest in distinct phenotypic outcomes. In our lab,
we propose to understand this phenomenon in the context of whether and how
the strains of low molecular weight oligomers could propagate their structure
faithfully towards morphologically distinct fibrils with conspicuous pathological
phenotypes. By biophysical investigations, we recently demonstrated that an
Aβ42 dodecamer called large fatty acid derived oligomers (LFAOs) is able to
quantitatively replicate at low concentrations and at elevated concentrations,
propagate their mesoscopic structure faithfully towards morphologically unique
fibrils containing the discrete LFAO units. Furthermore, LFAO-seeded aggregates
were able to selectively induce massive amounts of cerebral amyloid angiopathy
(CAA) in transgenic CRND8 mice as opposed to unseeded or fibril seeded
aggregates, which induced more parenchymal deposits. Results based on our
model oligomer demonstrate that certain oligomeric strains could faithfully
propagate their structure towards distinct fibrils and induce selective pathological
phenotypes in the brain. Overall, these results bring forth important mechanistic
insights into strain specific propagation of oligomers that have remained elusive
thus far.
Biography
Vijay Rangachari has completed his PhD from All India
Institute of Medical Sciences (AIIMS), New Delhi and
Postdoctoral Studies from Florida State University and
Mayo Clinic School of Medicine. He is currently the Chair of
the Chemistry and Biochemistry Department at University
of Southern Mississippi, a premier research and teaching
institution. He has publishedmore than 35 papers in reputed
journals and has been serving many publication houses.
vijay.rangachari@usm.eduCorrelation between oligomer conformation and
pathological variations in Alzheimer's disease
Vijay Rangachari
University of Southern Mississippi, USA
Vijay Rangachari et al., J Neurol Neurosci 2018, Volume: 2
DOI: 10.21767/2471-8548-C1-002