New models may improve Alzheimer’s research in people with Down syndrome and help test whether emerging treatments are safe.
The work aims to address a major gap in Alzheimer’s studies, as people with Down syndrome are often excluded from clinical trials despite their greatly increased risk.
Around 6m people globally live with Down syndrome, and it is estimated that about 90 per cent will develop Alzheimer’s in midlife.
Researchers led by Yann Herault, Fabio di Domenico and Dr Frances Wiseman developed two new mouse models of Down syndrome-related Alzheimer’s.
The work involved teams from Institut de Génétique Biologie Moléculaire et Cellulaire, Sapienza University of Rome and the UK Dementia Research Institute at UCL.
Down syndrome is a complex genetic condition caused by an extra copy of chromosome 21, meaning people have three copies rather than the usual two.
This creates an extra “dose” of all the genes on chromosome 21, which changes how the body works.
Down syndrome is the most common genetic cause of Alzheimer’s worldwide.
The average age for a person with Down syndrome to develop dementia symptoms is around 55, and dementia is the leading cause of death for adults over 35 with Down syndrome.
Dementia is a group of symptoms that can affect memory, thinking, behaviour and the ability to carry out daily activities.
Existing mouse models used to study this form of Alzheimer’s have limitations.
They usually involve three copies of a gene called APP, which produces amyloid beta, a protein implicated in Alzheimer’s disease.
But genetic differences in amyloid beta between mice and humans mean existing models do not form the same amyloid and tau clumps seen in the human disease.
Tau is another protein that can form tangles inside brain cells and is also linked to Alzheimer’s.
The new models include amyloid beta engineered to more closely resemble the human protein sequence.
The researchers said this allowed the mice to reproduce features of early Alzheimer’s.
The mice showed signs of memory problems, increased activity and more frequent risk-taking behaviour.
They also had changes in brain cells similar to early changes in Alzheimer’s in people with Down syndrome.
The researchers said the models could help improve understanding of the differences in Alzheimer’s experienced by people with Down syndrome.
They may also be useful for testing whether new Alzheimer’s drugs are safe for people with the condition, helping support more equitable treatment access.
People with Down syndrome have a greatly increased risk of Alzheimer’s, but are often excluded from trials of new therapies.
The researchers said better models could help close that equity gap and support future treatment development.