Sunday, January 24, 2016

Anti-PD1 antibody treatment shows beneficial effect in human Alzheimer disease (AD) mouse model

Michal Schwartz lab is famous in immunology circles for producing data showing the role of immune system in CNS function. For example, earlier their lab showed that mice deficient for adaptive immune system display decline in cognitive functions.

In this new paper the authors showed that two consecutive injections of anti-PD1 antibody (checkpoint inhibitor used in cancer immunotherapy) reduces CNS tissue pathology in mice with human AD phenotype [in two different models, (a) five familial AD mutations (5XFAD) and (b) APP/PS1 mouse models]. This beneficial effect correlated with the accumulation of peripheral macrophages into CNS and were dependent on IFN-γ.

It is not clear why systemic immune activation improves AD tissue pathology. Simple explanation is that peripheral "activated" macrophages that migrate to CNS are better equipped to digest and clean up AD-associated amyloid depositions. However, it is not clear whether CNS with AD pathology sends out any specific signals to recruit those peripheral macrophages or it is just nonspecific migration into CNS and other tissues [not examined in this paper].

David Usharauli 

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