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Page 8 of 24 Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019

commonly occur in Alzheimer’s disease and Alzheimer’s disease pathology is frequently found in Lewy
body diseases, but the extent of such co-pathologies across neurodegenerative diseases remains undefined.
The prevalences of proteinopathies of most neurodegenerative diseases were such that tau was nearly
universal, amyloid-β was common, α-synuclein was less common, and TDP-43 was the least common.
Recent development in cerebro-spinal fluid (CSF) biomarkers of neurodegenerative diseases demonstrated
that tau proteins (both total tau and phosphorylated-tau) increased and amyloid-β (Aβ42) decreased in
patients with Alzheimer’s disease; α-synuclein increased in patients with Parkinson’s disease; and so on.
Nevertheless, the collection of CSF is invasive and is not without risk. Thus, blood-based biomarkers
warrant further development. In our previous study, we developed a panel of plasma biomarkers by
using immunomagnetic reduction assay technology including Aβ42, Aβ40, total tau, phosphorylated-
tau, α-synuclein, phosphorylated α-synuclein, and TDP-43. Individual plasma biomarkers Aβ42 and
total tau and combined biomarkers such as Aβ42/Aβ40 and Aβ42/tau performed well in differentiating
older controls from patients with dementia due to Alzheimer’s disease. α-synuclein and phosphorylated
α-synuclein helped separate older controls from patients with Parkinson’s disease, as well as assisted
the differential diagnosis between Parkinson’s disease and other atypical Parkinsonism. In this study, we
demonstrated IMR assay results for Aβ42, total tau, phosphorylated-tau, α- synuclein, phosphorylated
α-synuclein, and TDP-43 in five groups of patients including control (n = 39), mild cognitive impairment
due to Alzheimer’s disease (n = 40), dementia due to Alzheimer’s disease (n = 34), Parkinson’s disease (n =
28), and frontotemporal dementia (n = 30). We demonstrated the capacity of IMR blood-based (plasma)
biomarkers in assisting diagnosis of individual neurodegenerative disease and showed the proteinopathy
co-pathology in the blood.

11. Critical role of brain-specific gangliosides in the pathogenesis of traumatic brain injury
and Alzheimer’s disease

Eugene D. Ponomarev, Marina Dukhinova, Ekaterina Kopeikina, Amanda W. Y. Yung, Tatyana
Veremeyko, Thomas Y. B. Lau

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

Major brain glycosphingolipids, also called brain gangliosides, are localized within neuronal lipid rafts
(NLR) of neuronal axons and synapses and their role in neurodegenerative diseases remains unknown.
Here, we compared the outcome of traumatic brain injury (TBI) and Alzheimer’s disease (AD) pathology in
wild-type and glycosphingolipid-deficient animals. The st3gal5 gene encodes for ST3 β-galactoside alpha-
2,3-sialyltransferase 5, which is responsible for the biosynthesis of complex a, b, and c series gangliosides
in the brain. We found that uninjured st3gal5-deficient mice exhibit normal cognitive and social behaviors,
but also exhibit some very mild motor deficits. After TBI, st3gal5-deficient animals exhibit marked deficits
in cognitive and motor functions, which was associated with increased hemorrhage and neuronal damage
owing to the failure of NLR-induced platelet activation and serotonin secretion. The decrease in NLR-
induced platelet-derived platelet activating factor release also resulted in reduced microglial activation
and central nervous system macrophage infiltration in the st3gal5-deficient animals after TBI. Further
investigation demonstrated that the interaction of platelets with NLR stimulated neurite growth, increased
the number of dendritic spines, and increased neuronal activity during TBI. To understand the role of
gangliosides in Alzheimer’s disease pathology, we crossed st3gal5-deficient mice with 5XFAD transgenic
mice that overexpress three mutant human amyloid proteins AP695 and two presenilin PS1 genes. We
found that st3gal5-deficient 5XFAD mice had a significantly reduced burden of amyloid depositions, low
level of neuroinflammation, and did not exhibit neuronal loss or synaptic dysfunction as compared to wild-