Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1
Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by β-amyloid (Aβ) accumulation in and around the cerebral blood vessels and capillaries and is highly comorbid with Alzheimer’s disease (AD). Familial forms of CAA result from mutations within the Aβ domain of the amyloid β pr...
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doaj-5fdadc0533d645aa9ca33b4dd1a5c1362020-11-25T03:49:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-03-01212348234810.3390/ijms21072348Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1Dominique L. Popescu0William E. Van Nostrand1John K. Robinson2Department of Psychology, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USAGeorge & Anne Ryan Institute for Neuroscience, University of Rhode Island, 130 Flagg Rd, Kingston, RI 02881, USADepartment of Psychology, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USACerebral amyloid angiopathy (CAA) is a small vessel disease characterized by β-amyloid (Aβ) accumulation in and around the cerebral blood vessels and capillaries and is highly comorbid with Alzheimer’s disease (AD). Familial forms of CAA result from mutations within the Aβ domain of the amyloid β precursor protein (AβPP). Numerous transgenic mouse models have been generated around expression of human AβPP mutants and used to study cerebral amyloid pathologies. While behavioral deficits have been observed in many AβPP transgenic mouse lines, relative to rats, mice are limited in behavioral expression within specific cognitive domains. Recently, we generated a novel rat model, rTg-DI, which expresses Dutch/Iowa familial CAA Aβ in brain, develops progressive and robust accumulation of cerebral microvascular fibrillar Aβ beginning at 3 months, and mimics many pathological features of the human disease. The novel rTg-DI model provides a unique opportunity to evaluate the severity and forms of cognitive deficits that develop over the emergence and progression of CAA pathology. Here, we present an in-depth, longitudinal study aimed to complete a comprehensive assessment detailing phenotypic disease expression through extensive and sophisticated operant testing. Cohorts of rTg-DI and wild-type (WT) rats underwent operant testing from 6 to 12 months of age. Non-operant behavior was assessed prior to operant training at 4 months and after completion of training at 12 months. By 6 months, rTg-DI animals demonstrated speed–accuracy tradeoffs that later manifested across multiple operant tasks. rTg-DI animals also demonstrated delayed reaction times beginning at 7 months. Although non-operant assessments at 4 and 12 months indicated comparable mobility and balance, rTg-DI showed evidence of slowed environmental interaction. Overall, this suggests a form of sensorimotor slowing is the likely core functional impairment in rTg-DI rats and reflects similar deficits observed in human CAA.https://www.mdpi.com/1422-0067/21/7/2348cerebral amyloid angiopathyAlzheimer’s diseaserat modeloperant testingradial arm mazenovel object recognition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dominique L. Popescu William E. Van Nostrand John K. Robinson |
spellingShingle |
Dominique L. Popescu William E. Van Nostrand John K. Robinson Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1 International Journal of Molecular Sciences cerebral amyloid angiopathy Alzheimer’s disease rat model operant testing radial arm maze novel object recognition |
author_facet |
Dominique L. Popescu William E. Van Nostrand John K. Robinson |
author_sort |
Dominique L. Popescu |
title |
Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1 |
title_short |
Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1 |
title_full |
Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1 |
title_fullStr |
Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1 |
title_full_unstemmed |
Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1 |
title_sort |
longitudinal cognitive decline in a novel rodent model of cerebral amyloid angiopathy type-1 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-03-01 |
description |
Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by β-amyloid (Aβ) accumulation in and around the cerebral blood vessels and capillaries and is highly comorbid with Alzheimer’s disease (AD). Familial forms of CAA result from mutations within the Aβ domain of the amyloid β precursor protein (AβPP). Numerous transgenic mouse models have been generated around expression of human AβPP mutants and used to study cerebral amyloid pathologies. While behavioral deficits have been observed in many AβPP transgenic mouse lines, relative to rats, mice are limited in behavioral expression within specific cognitive domains. Recently, we generated a novel rat model, rTg-DI, which expresses Dutch/Iowa familial CAA Aβ in brain, develops progressive and robust accumulation of cerebral microvascular fibrillar Aβ beginning at 3 months, and mimics many pathological features of the human disease. The novel rTg-DI model provides a unique opportunity to evaluate the severity and forms of cognitive deficits that develop over the emergence and progression of CAA pathology. Here, we present an in-depth, longitudinal study aimed to complete a comprehensive assessment detailing phenotypic disease expression through extensive and sophisticated operant testing. Cohorts of rTg-DI and wild-type (WT) rats underwent operant testing from 6 to 12 months of age. Non-operant behavior was assessed prior to operant training at 4 months and after completion of training at 12 months. By 6 months, rTg-DI animals demonstrated speed–accuracy tradeoffs that later manifested across multiple operant tasks. rTg-DI animals also demonstrated delayed reaction times beginning at 7 months. Although non-operant assessments at 4 and 12 months indicated comparable mobility and balance, rTg-DI showed evidence of slowed environmental interaction. Overall, this suggests a form of sensorimotor slowing is the likely core functional impairment in rTg-DI rats and reflects similar deficits observed in human CAA. |
topic |
cerebral amyloid angiopathy Alzheimer’s disease rat model operant testing radial arm maze novel object recognition |
url |
https://www.mdpi.com/1422-0067/21/7/2348 |
work_keys_str_mv |
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