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September 16-17, 2019 | Paris, France

Dementia and Alzheimer's Disease

World Congress on

Journal of Clinical Psychiatry and Cognitive Psychology | Volume: 03

Human plasma HDL prevents the formation of α-synuclein oligomers and fibrils

Giovanni Bellomo, Sara Bologna, Linda Cerofolini, Silvia Paciotti, Leonardo Gatticchi, Enrico Ravera, Lucilla

Parnetti, Marco Fragai and Claudio Luchinat

Magnetic Resonance Centre (CERM), University of Florence, Italy

igh-density lipoproteins (HDL) are the smallest

particles among the five major groups of lipoproteins.

The most abundant protein constituents of HDL in central

nervous system are apolipoprotein-A1 (apoA1) and

apolipoprotein-E (apoE). The APOE-ε4 allele is strongly

associated with the sporadic late-onset of Alzheimer’s

Disease. Conversely, no association has been found

between apoE and Parkinson’s Disease (PD). ApoA1 is the

main component of HDL in plasma but it is also necessary

for cholesterol transportation in the central nervous

system. Lower levels of apoA1 were rather measured in

the plasma of PD patients with respect to controls. Lower

levels of apoA1 were found to be associated with the age of

PD onset and severity of motor symptoms in 254 research

volunteers enrolled in the Parkinson's Progression Markers

Initiative (PPMI), suggesting that apoA1-rich lipoproteins

may be both a protective factor and a candidate biomarker

for PD. In our work we investigated the protective

role of apoA1-rich HDL against alpha-synuclein (α-syn)

aggregation by Thioflavin-T fluorescence, NMR and

conformational antibodies. In our experiments human

plasma HDL strongly inhibited the formation of fibrillary

and oligomeric aggregates produced by α-syn. Conversely,

we did not observe any relevant interaction between

monomeric α-syn and HDL from NMR experiments. These

findings suggest that the antiaggregatory effect of HDL and

α-syn may involve an interaction with α-syn oligomeric

intermediates, by preventing them to grow and to convert

into fibrillar amyloids.