Study leads to potential for new treatment approach for Alzheimer's


Date:
August 25, 2020
Source:
University of Kentucky
Summary:
Research looking at a possible new therapeutic approach for
Alzheimer's disease focuses on targeting inflammation by using
an antibody.



FULL STORY ========================================================================== Research looking at a possible new therapeutic approach for Alzheimer's
disease was recently published in the Journal of Neuroinflammation. The
paper out of the University of Kentucky's Sanders-Brown Center on
Aging (SBCoA) is titled "Therapeutic Trem2 activation ameliorates
amyloid-beta deposition and improves cognition in the 5XFAD model
of amyloid deposition." The work looked at targeting inflammation by
using an antibody. Alzheimer's disease and related dementias have no disease-modifying treatments at this time and represent a looming public
health crisis given the continually growing aging population.


==========================================================================
The paper explains that current therapeutic approaches to the treatment
of Alzheimer's disease focus on the major pathological hallmarks of
the disease which are amyloid plaques and neurofibrillary tangles. They
are the requirements for a diagnosis of Alzheimer's disease. However,
the authors say there has been an explosion of genetic data suggesting
the risk for sporadic Alzheimer's disease is driven by several other
factors including neuroinflammation, membrane turnover and storage,
and lipid metabolism.

In this study the researchers focused on triggering receptor expressed
on myeloid cell-2 (TREM2). "TREM2 was identified several years ago as
a gene that, when there's a mutation, significantly increases risk of Alzheimer's disease.

The field thinks that this mutation reduces the function of the receptor,
so we hypothesized that targeting TREM2 to increase its function might
be a valid treatment for Alzheimer's," explained Donna Wilcock, SBCoA
associate director.

Through the groups work they found that the therapeutic targeting of TREM2 using a TREM2-activating antibody leads to the activation of microglia, recruitment of microglia to amyloid plaques, reduced amyloid deposition,
and ultimately improved cognition. "The big takeaway is that this is
the first approach that targets TREM2 to promote microglia to clear
the amyloid deposits in the brain that are thought to be the cause of Alzheimer's," said Wilcock.

The biopharmaceutical company Alector developed the antibody for this
study which was conducted on mice. Due to the study's success SBCoA is
set to be a site for an upcoming clinical trial using this new approach.

This work was supported by the National Institutes of Health NIA grant
awarded to Donna Wilcock PhD: RO1AG057754. Predoctoral fellow Brittani
Price was supported by the NIH-NINDS T32 NS077889, Neurobiology of CNS
Injury & Repair.


========================================================================== Story Source: Materials provided by University_of_Kentucky. Original
written by Hillary Smith. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika
Johnson,
Danielle Hawthorne, Abigail Woolums, Donna M. Wilcock. Therapeutic
Trem2 activation ameliorates amyloid-beta deposition and improves
cognition in the 5XFAD model of amyloid deposition. Journal of
Neuroinflammation, 2020; 17 (1) DOI: 10.1186/s12974-020-01915-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200825110807.htm

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