PORTFOLIO

Alzheimer disease is the most common form of dementia in the western world for which to date no curative treatment is available. Furthermore there is no early, objective and definitive diagnosis of Alzheimer’s disease in patients. This project relies on an unexpected discovery based upon the use of waste products for the detection of Alzheimer’s disease in living mammals. Exploiting these findings is intended for bringing to the market a simple, fast, non-invasive and cost-effective molecular diagnostic concept of this devastating disorder.

The absence of objective and early diagnosis considerably limits the identification of Alzheimer patients for drug testing by pharmaceutical industries. Providing a simple and non-invasive test will facilitate and reduce the duration of the diagnostic.

Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease animals with intestinal microbiota. Sequencing bacterial 16S rRNA from fecal samples revealed a remarkable shift in the gut microbiota of conventionally-raised Alzheimer's disease mice as compared to healthy, wild-type mice. Colonization of germ-free Alzheimer mice with harvested microbiota from conventionally-raised Alzheimer mice dramatically increased cerebral Ab pathology. In contrast, colonization with microbiota from control wild-type mice was ineffective in increasing cerebral Ab levels. Our results indicate a microbial involvement in the development of Alzheimer's disease pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.

Alzheimer’s disease is a neurodegenerative disorder not only affecting more and more the elderly population but also representing an ever-growing burden to our society.

In this context, the GRS funded project (Alzheimer diagnosis in waste products) tried to establish a novel diagnostic tool based on a readout of human waste products.

Surprisingly, these initial findings opened the door to a much larger view into Alzheimer’s disease. The microbiome of our gut i.e. the bacterial content of our intestine shows a significant shift of the bacterial profile related to AD. Besides a novel diagnostic tool, a number of additional risk factors may be defined. The most surprising finding is a potential delay for the onset of AD when reversing or modulating the AD related changes of the bacterial profile.

The GRS funding have been an essential contribution for the initiation and the first experimental finding which have been very recently largely expanded involving a multidisciplinary European Consortium working jointly on a novel project called "AD-gut" for pursuing and expanding this novel and unexpected road for innovative diagnosis and its potential novel therapy for these diseases like AD and maybe for more as closely related neurodegenerative and metabolic disorders.

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