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We investigated the potential mechanisms through which Cerebrolysin™, a neuroprotective noothropic agent, might affect Alzheimer’s disease pathology. Transgenic (tg) mice expressing mutant human (h) amyloid precursor protein 751 (APP751) cDNA under the Thy-1 promoter (mThyl-hAPP751) were treated for four weeks with this compound and analyzed by confocal microscopy to asses its effects on amyloid plaque formation and neurodegeneration. In this model, amyloid plaques in the brain are found much earlier (beginning at 3 months) than in other tg models. Quantitative computer-aided analysis with anti-amyloid-β protein (Aβ) antibodies, revealed that Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Furthermore, Cerebrolysin treatment reduced the levels of Aβ1–42. This was accompanied by amelioration of the synaptic alterations in the frontal cortex of mThyl-hAPP751 tg mice. In conclusion, the present study supports the possibility that Cerebrolysin might have neuroprotective effects by decreasing the production of Af and reducing amyloid deposition.

Excitotoxicity might play an important role in neurodegenerative disorders such as Alzheimer’s disease. In the mouse brain, kainic acid (KA) lesioning results in neurodegeneration patterns similar to those found in human disease. For this study, two sets of experiments were performed in order to determine if Cerebrolysin™ ameliorates the alterations associated with KA administration. In the first set of experiments, mice received intraperitoneal KA injections followed by Cerebrolysin™ administration, while in the second, mice were pretreated with Cerebrolysin™ for 4 weeks and then challenged with KA. Behavioral testing in the water maze and assessment of neuronal structure by laser scanning confocal microscopy showed a significant protection against KA lesions in mice pretreated with Cerebrolysin™. In contrast, mice that received Cerebrolysin™ after KA injections did not show significant improvement. This study supports the contention that Cerebrolysin™ might have a neuroprotective effect in vivo against excitotoxicity.