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Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes.
Brain Res. 2004 Aug 13; 1017(1-2):130-6.BR

Abstract

Several transgenic mouse models of Alzheimer's disease (AD) have been developed that exhibit beta-amyloid (Abeta) neuropathology and behavioural deficits. However, not all studies have investigated the relationship between the development of cognitive impairment and neuropathology. Therefore, temporal changes in cognition were investigated in male and female double-mutant APPswexPS1.M146V (TASTPM) transgenic mice using an object recognition test and correlated with the development of cerebral Abeta neuropathology. Both male and female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and 10 months of age in the object recognition test, compared to wild-type littermates. There was no such cognitive impairment at 3 or 4 months of age. Quantitative immunohistochemistry using a battery of Abeta antibodies demonstrated that cerebral Abeta deposition was first apparent in 3-month-old mice, and it increased with age. The early appearance of cerebral Abeta deposits in the double-transgenic TASTPM mice supports the evidence that mutations in the PS1 gene accelerate Abeta deposition. The cerebral Abeta load was greater in female than in male TASTPM mice at all ages investigated. In the electron microscope, mature Abeta plaques comprising a fibrillar core surrounded by degenerating neurites and reactive glia were first observed in the cortex of TASTPM mice at 6 months of age, the same age at which cognitive impairment became apparent. These results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Abeta deposition, which first occurs 3 months earlier.

Authors+Show Affiliations

Neurology and GI CEDD, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK. david_howlett-1@gsk.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15261108

Citation

Howlett, David R., et al. "Cognitive Correlates of Abeta Deposition in Male and Female Mice Bearing Amyloid Precursor Protein and Presenilin-1 Mutant Transgenes." Brain Research, vol. 1017, no. 1-2, 2004, pp. 130-6.
Howlett DR, Richardson JC, Austin A, et al. Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Res. 2004;1017(1-2):130-6.
Howlett, D. R., Richardson, J. C., Austin, A., Parsons, A. A., Bate, S. T., Davies, D. C., & Gonzalez, M. I. (2004). Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Research, 1017(1-2), 130-6.
Howlett DR, et al. Cognitive Correlates of Abeta Deposition in Male and Female Mice Bearing Amyloid Precursor Protein and Presenilin-1 Mutant Transgenes. Brain Res. 2004 Aug 13;1017(1-2):130-6. PubMed PMID: 15261108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. AU - Howlett,David R, AU - Richardson,Jill C, AU - Austin,Angela, AU - Parsons,Andrew A, AU - Bate,Simon T, AU - Davies,D Ceri, AU - Gonzalez,M Isabel, PY - 2004/05/10/accepted PY - 2004/7/21/pubmed PY - 2004/10/5/medline PY - 2004/7/21/entrez SP - 130 EP - 6 JF - Brain research JO - Brain Res VL - 1017 IS - 1-2 N2 - Several transgenic mouse models of Alzheimer's disease (AD) have been developed that exhibit beta-amyloid (Abeta) neuropathology and behavioural deficits. However, not all studies have investigated the relationship between the development of cognitive impairment and neuropathology. Therefore, temporal changes in cognition were investigated in male and female double-mutant APPswexPS1.M146V (TASTPM) transgenic mice using an object recognition test and correlated with the development of cerebral Abeta neuropathology. Both male and female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and 10 months of age in the object recognition test, compared to wild-type littermates. There was no such cognitive impairment at 3 or 4 months of age. Quantitative immunohistochemistry using a battery of Abeta antibodies demonstrated that cerebral Abeta deposition was first apparent in 3-month-old mice, and it increased with age. The early appearance of cerebral Abeta deposits in the double-transgenic TASTPM mice supports the evidence that mutations in the PS1 gene accelerate Abeta deposition. The cerebral Abeta load was greater in female than in male TASTPM mice at all ages investigated. In the electron microscope, mature Abeta plaques comprising a fibrillar core surrounded by degenerating neurites and reactive glia were first observed in the cortex of TASTPM mice at 6 months of age, the same age at which cognitive impairment became apparent. These results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Abeta deposition, which first occurs 3 months earlier. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15261108/Cognitive_correlates_of_Abeta_deposition_in_male_and_female_mice_bearing_amyloid_precursor_protein_and_presenilin_1_mutant_transgenes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006899304007760 DB - PRIME DP - Unbound Medicine ER -