Non-invasive infra-red therapy (1072 nm) reduces β-amyloid protein levels in the brain of an Alzheimer’s disease mouse model, TASTPM

BackgroundAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease and common cause of dementias in the Western world. This study investigated the expression profile of heat-shock proteins (HSPs) involved in maintaining healthy neurons in the TASTPM AD mouse model, and whether chronic treatment with 1072 nm infra-red (IR1072) modified the expression profiles of HSPs and amyloidopathy in female TASTPM mice.Methodology/principal findingsQuantitative immunoblotting and immunohistochemistry were used to examine the expression of proteins such as HSPs, phosphorylated tau (tau-P), amyloid precursor protein (APP), β-amyloid1–40 (Aβ), and Aβ1–42. TASTPM mice at 3, 7 and 12 months were investigated as well as female TASTPM mice which had undergone a chronic, 5 month, IR1072 treatment. During the first 12 months of age, a critical period of AD progression, reduced HSP40 and HSP105 were observed. αB-crystallin, Aβ1–42 and tau-P increased over this period, particularly between 3 and 7 months. Chronic IR1072 treatment of female TASTPM mice elicited significant increases in HSP60, 70 and 105 and phosphorylated-HSP27 (P-HSP27) (50–139%), together with a concomitant profound decrease in αB-crystallin, APP, tau-P, Aβ1–40 and Aβ1–42 (43–81%) protein levels at 7 months of age. Furthermore, IR1072 treatment elicited a modest, but significant, reduction in Aβ1–42 plaques in the cerebral cortex.Conclusions/significant findingsIR1072 treatment provides a novel non-invasive and safe way to upregulate a panel of stress response proteins in the brain, known to both reduce protein aggregation and neuronal apoptosis. This approach recently entered clinical trials for AD in the USA, and may provide a novel disease modifying therapy for a range of neuropathologies.

► Behavioural deficits coincide with higher aB-crystallin, Aβ and tau-P levels.
► IR1072 exposure elicited differential changes in HSPs with neuroprotective properties.
► IR1072 exposure produced a parallel reduction in αB crystallin and Aβ(1-42) levels.
► IR1072 exposure elicited a reduction tau-P independent of GSK-3β.