Alzheimer\\\\\\\'s disease is a neurodegenerative disorder characterized by slowly progressive dementia, with the hallmark of beta-amyloid peptides (Aβ) as the main constituent of the senile plaques. Aβ 1–42 is one of the enzymatic cleavage fragments of the amyloid precursor protein, which exerts direct neurotoxic effects. Herein, we introduced a murine model of Alzheimer\\\\\\\'s disease by microsurgically implantation of fibrillar Aβ 1–42 into the CA1 region of the mouse hippocampus. Twelve-week-old male mice were anesthetized under isoflurane. Bilateral infusions of 1 mM fibrillar Aβ 1–42 (n =7) or PBS (n = 7) were made stereotaxically into the dorsal hippocampus (2.5 mm posterior; ±2 mm lateral; 1.4 mm ventral), using 31-gauage cannulae connected by PE tubing to 5-µl Hamilton syringes mounted on a Hamilton syringe drive at a rate of 0.4 µl/min over a period of 5 min. The cannulae were left in place for 10 min before being slowly withdrawn. Animals were allowed to recover for 1 wk before behavioral testing. Acquisition of spatial learning and memory were assessed using the Morris water maze task. The apparatus was a circular tank 123 cm in diameter, 35 cm deep, raised 60 cm from the floor, and filled to a height of ~21.5 cm with 22°C water made opaque by the addition of skim milk powder. A 10×10-cm escape platform was submerged 1.5 cm below the surface of the water, positioned in the middle of the northeast quadrant. All mice received two blocks of four swimming trials each day, for 4 consecutive days. For each trial block, animals were released from each of the four cardinal compass points and allowed to swim freely until they climbed onto the platform. Swim paths were recorded and analyzed using the 2020 Plus tracking system for the Morris water maze (HVS Image). Data were analyzed using a repeated measures ANOVA (Statview 5; SAS Institute). The results revealed increased swim path and also delayed escape time in Aβ 1–42 -implanted group compared to the PBS-implanted mice. This introduces a new microsurgically method for inducing age-related neurodegenerative disorders in animal models.

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