Olfactory stem cells for investigating the causes and progression of dementia

BACKGROUND

With no clinical success yet achieved from amyloidtargeting strategies, there is an urgent need to gain new insights and develop effective treatments for people who have dementia. New stem cell-based approaches have generated much excitement in dementia research with the potential to study patient-derived neurons and supporting cells. However, the commonly used ‘pluripotent’ stem cells are artificially generated and do not possess all needed cell types, which makes them unsuitable as tools to understand the disease process in the majority of lateonset (sporadic) cases of dementia.

Olfactory (nasal) tissue contains a unique population of naturally occurring stem cells that renew the nasal receptor neurons and supporting cells in the nose throughout life. These exceptional stem cells can be collected through a routine procedure with local anaesthetic and readily grown in a culture dish in a laboratory to produce neurons and other key brain cell types that accurately reflect the same types of brain cells that occur in the patient of origin. These cells provide a unique tool to study patient-specific disease processes and develop therapeutics for personalised dementia medicine.

OBJECTIVE

Our plan is to collect nasal tissue from people with
dementia and from people who are at high risk for
dementia (together with matching control samples). The
olfactory stem cells will be grown in our lab and studied
using a range of molecular approaches to provide unique
insights into the early disease changes in a person’s brain
cells. We are also attempting to grow brain organoids
from stem cells. These are ‘mini-brains’ that represent
the 3-dimensional structure of a small part of a human
brain and allow a much more accurate understanding of
how brain cells work (or fail to work) in dementia. This will
enable us to understand how brain cells are affected by
dementia differently for each patient (i.e., derived neurons
will retain patient-specific epigenetic markers) and will
allow the screening of