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Beyond Amyloid Hypothesis: a novel approach to fight Alzheimer's Disease

Project objectives

In the latest World Report on Alzheimer's Disease the global economic impact of Alzheimer's disease (AD) and dementias was estimated at $818 billion with 47 million people living with AD, 0,5% of the world's population. Despite this need, there is currently no prevention, cure or even therapy to delay the progression of the disease. No significant new drugs for AD have been approved in the past 15 years, despite hugely expensive studies aimed at tackling the disease.

An often cited explanation for the failure of clinical trials is that they are set up too late in the disease process; this notion is also probable for anti-amyloid-β immunotherapy. Another crucial point that could explain the failure of a clinical trial is evidence of an existing multiplicity of "causes" or risk factors in the etiology of AD, raising the question of whether AD is a unitary disease for which only one drug is effective. It is therefore necessary to go beyond the formation of plaques and tangles to more fully recapitulate the events observed in a diseased brain.

In recent years, the role of a subcortical region of the brain rich in dopaminergic neurons, the ventral tegmental area (VTA), has emerged as a brain area particularly susceptible to disease mechanisms.

The goal of this project is translational research, from the AD mouse model to AD patients, targeting VTA dopamine neurons.

The objectives of this project are:

  • Evaluate whether loss of DA from the VTA and/or Locus coeruleus is sufficient to induce AD, in the absence of Aβ overexpression.
  • To evaluate why some dopaminergic neurons are more vulnerable than others to degeneration
  • Modifying the autophagic process in AD animals can delay or block cell death
  • To evaluate whether genistein, a drug that modulates the autophagic process, has beneficial outcomes in patients with MCI.

Start and end date

September 2020 - August 2023

Project Manager

Prof. Marcello D'Amelio, Coordinator

Coordinating institution of the project

Università Campus Bio-Medico di Roma

Other Institutions involved

  • Campus Bio-Medico University Hospital Foundation
  • IRCCS Santa Lucia Foundation, Rome

Funding source

Rome Foundation (Rome, Italy)

Economic value of the project

€ 735.000

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