Selene Lomoio

Alzheimer's disease (AD) accounts for approximately 70% of all cases of dementia. Currently,
no cure or prevention for AD exists. During my predoctoral career, I conducted innovative
studies on sporadic and familial AD mouse models aimed to elucidate the role of cerebellum in
this pathology. Since I joined Dr. G. Tesco laboratory, I have been trying to comprehend the
function of the protein GGA3 in both healthy and AD brains. I developed and advanced an
innovative live cell imaging approach to investigate GGA3 trafficking in hippocampal neurons. I
recently demonstrated that not only does GGA3 reside in axons, but fundamentally that this
protein is essential for BACE1 trafficking regulation and homeostasis. Our current data
demonstrate that GGA3 genetic deletion results in the accumulation of BACE1 in the axon of
hippocampal neurons. Furthermore, we observed a general disruption of BACE1 axonal
trafficking in GGA3 null neurons together with its accumulation in axonal swellings. We have
also identified a novel AD-linked GGA3 loss of function mutation in late-onset AD patients.
Altogether, our data demonstrate that GGA3 loss of function and consequent axonal
accumulation of BACE1 initiate a cascade of events leading to AD-like axonopathy. Our studies
provide a proof-of-concept that drugs aimed to preserve GGA3 function could be beneficial for
AD treatment and/or prevention. Recently, I have been developing a new experimental approach
to differentiate human neurons from iPSC derived from patient carrying familial AD mutations. I
have already established a successful protocol to differentiate 2D iPSC-derived neuronal culture
from these lines. Currently, I am collaborating with Dr. D. Kaplan to grow these neurons in silk-collagen
protein scaffolds. This model is highly innovative. Differentiating neurons will grow in
a donut-shaped porous silk sponge within an optically cleared collagen-filled central region
which will allow, for the first time, live in vivo studies of a human Alzheimer's brain-like tissue
during ageing under controlled experimental conditions.