{Reference Type}: Journal Article
{Title}: Androgen deprivation therapy exacerbates Alzheimer's-associated cognitive decline via increased brain immune cell infiltration.
{Author}: Zhang C;Aida M;Saggu S;Yu H;Zhou L;Rehman H;Jiao K;Liu R;Wang L;Wang Q;
{Journal}: Sci Adv
{Volume}: 10
{Issue}: 25
{Year}: 2024 Jun 21
{Factor}: 14.957
{DOI}: 10.1126/sciadv.adn8709
{Abstract}: Androgen deprivation therapy (ADT) for prostate cancer is associated with an increased risk of dementia, including Alzheimer's disease (AD). The mechanistic connection between ADT and AD-related cognitive impairment in patients with prostate cancer remains elusive. We established a clinically relevant prostate cancer-bearing AD mouse model to explore this. Both tumor-bearing and ADT induce complex changes in immune and inflammatory responses in peripheral blood and in the brain. ADT disrupts the integrity of the blood-brain barrier (BBB) and promotes immune cell infiltration into the brain, enhancing neuroinflammation and gliosis without affecting the amyloid plaque load. Moreover, treatment with natalizumab, an FDA-approved drug targeting peripheral immune cell infiltration, reduces neuroinflammation and improves cognitive function in this model. Our study uncovers an inflammatory mechanism, extending beyond amyloid pathology, that underlies ADT-exacerbated cognitive deficits, and suggests natalizumab as a potentially effective treatment in alleviating the detrimental effects of ADT on cognition.