Transcranial laser therapy (TLT) was tested for efficacy in a mouse model of Alzheimer's disease (AD) using a near-infrared energy laser system. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal function. Studies were performed to determine the effect of TLT in an amyloid-β protein precursor (AβPP) transgenic mouse model. TLT was administered 3 times/week at various doses, starting at 3 months of age, and was compared to a control group (no laser treatment). Treatment was continued for a total of six months. Animals were examined for amyloid load, inflammatory markers, brain amyloid-β (Aβ) levels, plasma Aβ levels, cerebrospinal fluid Aβ levels, soluble AβPP (sAβPP) levels, and behavioral changes. The numbers of Aβ plaques were significantly reduced in the brain with administration of TLT in a dose-dependent fashion. Administration of TLT was associated with a dose-dependent reduction in amyloid load. All TLT doses mitigated the behavioral effects seen with advanced amyloid deposition and reduce the expression of inflammatory markers in the AβPP transgenic mice. All TLT doses produced an increase in sAβPPα and a decrease in CTFβ levels consistent with inhibition of the β-secretase activity. In addition, TLT showed an increase in ATP levels, mitochondrial function, and c-fos suggesting an overall improvement in neurological function. These studies suggest that TLT is a potential candidate for treatment of AD.