Each transgenic mouse model of AD provides different insights into aspects of AD pathology and progression. Careful forethought is therefore required in the selection of an optimal model based on specific research interests. Our hope is that, with regard to motor and cognitive selleck chemicals deficits relating to AD, the discussion and Figure ?Figure44 presented here can help in the selection of the ideal model by providing an overview of the development and time course of behavioral deficits in the commonly used mouse models of AD. Conclusion This study is the first comprehensive behavioral analysis reported for the APP/PS1 KI mouse model of AD and the results presented here add to a growing literature for this model.
The lack of any motor/coordination deficits or abnormal anxiety levels, coupled with an age/disease-related cognitive decline and the high physiological relevance of this model, make it well suited for utilization in preclinical testing of AD-relevant therapeutics. Abbreviations AD: Alzheimer’s disease; APP: amyloid precursor protein; D2: discrimination index; KI: knock-in; NADPH: nicotinamide adenine dinucleotide phosphate; NOR: novel object recognition; PS-1: presenilin-1; RAWM: radial arm water maze; WT: wild type Competing interests The authors declare that they have no competing interests. Authors’ contributions SJW participated in the design of the research studies, performed the behavioral tests, and drafted the manuscript. ADB participated in the design of the study, performed the statistical analyses, and helped analyze data and draft the manuscript.
LJVE conceived of the Batimastat study, participated in its design and coordination, and helped write the manuscript. All authors read and approved the final manuscript. Acknowledgements The authors thank Danielle Goulding for maintenance of the mouse colonies and excellent technical sellekchem assistance. This research was supported in part by National Institutes of Health grants R01 NS064247 (LJVE), P01 “type”:”entrez-nucleotide”,”attrs”:”text”:”AG005119″,”term_id”:”2865077″,”term_text”:”AG005119″AG005119 (LJVE), and F32 “type”:”entrez-nucleotide”,”attrs”:”text”:”AG037280″,”term_id”:”16564153″,”term_text”:”AG037280″AG037280 (ADB), and by the Edward N. & Della L. Thome Memorial Foundation Awards Program in Alzheimer’s Disease Drug Discovery Research (LJVE).
One of the barriers to understanding the heterogeneity in these early populations is the difficulty in isolating cognitive domains for measurement. Most neuropsychological (NP) tests require a number of cognitive processes and, therefore, measures of multiple domains.