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Zaragoza, Spain

Rosado B.,University of Zaragoza | Gonzalez-Martinez A,University of Santiago de Compostela | Pesini P.,Araclon Biotech Ltd. | Garcia-Belenguer S.,University of Zaragoza | And 5 more authors.
Veterinary Journal | Year: 2012

Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it is considered a natural model for Alzheimer's disease in humans. Changes in spontaneous activity (including locomotor and exploratory behaviour) and social responsiveness have been related to the age and cognitive status of kennel-reared Beagle dogs. The aim of this study was to assess the influence of age and severity of CDS on locomotor and exploratory behaviour of privately owned dogs. This is the first part of a two-part report on spontaneous activity in pet dogs.An open-field (OF) test and a curiosity test were administered at baseline and 6. months later to young (1-4. years, n= 9), middle-aged (5-8. years, n= 9), cognitively unimpaired aged (≥9. years, n= 31), and cognitively impaired aged (≥9. years, n= 36) animals. Classification of cognitive status was carried out using an owner-based observational questionnaire, and in the cognitively impaired group, the dogs were categorised as having either mild or severe cognitive impairment. Dogs were recorded during sessions in the testing room and the video-recordings were subsequently analysed.The severity of CDS (but not age) influenced locomotion and exploratory behaviour so that the more severe the impairment, the higher the locomotor activity and frequency of corner-directed (aimless) behaviours, and the lower the frequency of door-aimed activities. Curiosity directed toward novel stimuli exhibited an age-dependent decline although severely affected animals displayed more sniffing episodes directed towards the objects. OF activity did not change after 6. months. Testing aged pet dogs for spontaneous behaviour might help to better characterise cognitively affected individuals. © 2012 Elsevier Ltd.

Sarasa L.,Araclon Biotech Ltd. | Allue J.A.,Araclon Biotech Ltd. | Pesini P.,Araclon Biotech Ltd. | Gonzalez-Martinez T.,University of Santiago de Compostela | And 2 more authors.
Neurobiology of Aging | Year: 2013

It is well known that several Aβ species, including Aβ40 and Aβ42, are present in cerebrospinal fluid (CSF). Experimental results suggest that these species could play a role in Alzheimer's disease and might also have diagnostic significance. In the present work, the canine CSF β-amyloid species profile has been identified by matrix-assisted laser desorption and ionization-time-of-flight/time of flight mass spectrometry (MALDI-TOF/TOF) analysis after immunoprecipitation with different Aβ-specific antibodies. Theresults show that species arising from combined β- and γ-secretase activities in humans, such as Aβ1-33, Aβ1-34, Aβ1-37, Aβ1-38, Aβ1-39, Aβ1-40, and Aβ1-42, are also present in dogs. Species arising from combined α- and β-secretase activities, as well as other Aβ-degrading enzymes, are also present in both human and canine CSF, with the exception of Aβ1-13, Aβ1-14, and Aβ1-18, which are not detected in dogs. A large number of species truncated at Glu-3 and Glu-11 have also been detected. To our knowledge, this work describes a most complete Aβ species profile from canine CSF. The similarities between the canine and human CSF Aβ profile reinforce the dog as a highly appropriate animal model for research in Alzheimer's disease. © 2013 Elsevier Inc.

Perez-Grijalba V.,Araclon Biotech Ltd. | Pesini P.,Araclon Biotech Ltd. | Monleon I.,Araclon Biotech Ltd. | Boada M.,Institute Catala Of Neurciencies Aplicades | And 6 more authors.
Journal of Alzheimer's Disease | Year: 2013

Validation of cost-effective, non-invasive methods to identify early (pre-clinical) Alzheimer's disease (AD) is increasingly becoming a key research challenge. We have developed two ELISA sandwich colorimetric tests for the accurate detection of amyloid-β (Aβ)1-40 and Aβ1-42: i) directly accessible (DA) in the plasma, ii) recovered from the plasma sample (RP) after diluting the plasma sample in a formulated buffer, and iii) associated with the remaining cellular pellet (CP). These tests were carried out on samples from healthy controls (n = 19) and individuals with mild cognitive impairment (MCI; n = 27) with amnestic-hippocampal syndrome to investigate whether this comprehensive approach may help to explain the association between blood Aβ levels and MCI. A logistic regression analysis detected seven direct or calculated markers (CP 40, DA 42, RP 42, DA/CP 40, DA/RP 42, DA/CP 42, and DA 42/40) with significant odds ratios (OR) after they were dichotomized with regard to the median of the pooled population. In particular, the likelihood [OR (95% CI)] of having MCI for patients with catCP 40, catDA/RP 42, catDA/CP 42, or catDA 42/40 below the corresponding population median ('positive test') was 11.48 (1.87-70.52), 22.09 (3.19-152.61), 11.48 (1.87-70.50), and 9.54 (1.77-51.38)-fold higher, respectively, than in those with a 'negative test' after adjusting for the effect of the ApoE genotype. These results are congruent with the hypothesis that changes in blood Aβ levels may be associated with the initial stages of AD. Thus, these Aβ blood biomarkers might be useful tools for screening for those at increased risk of developing AD. © 2013 - IOS Press and the authors. All rights reserved.

Gonzalez-Martinez A.,University of Santiago de Compostela | Rosado B.,University of Zaragoza | Pesini P.,Araclon Biotech Ltd. | Suarez M.-L.,University of Santiago de Compostela | And 5 more authors.
Experimental Gerontology | Year: 2011

Aging dogs naturally demonstrate cognitive impairment and neuropathology that model early Alzheimer's disease (AD). In particular, there is evidence that canine cognitive dysfunction syndrome (CDS) in aged dogs is accompanied by cortical deposition of Aβ peptides and neurodegeneration. Plasma Aβ levels have been examined in humans as putative biomarkers for AD, but to date, no similar studies have been conducted for canine dementia. The aim of the present study was to assess plasma Aβ1-42 and Aβ1-40 levels in a blind study using pet dogs that were either successfully aging or exhibiting CDS. The severity of cognitive impairment was assessed using an owner-based questionnaire. On average, young dogs presented significantly higher plasma levels of Aβ1-42 and Aβ1-40 than aged, cognitively unimpaired dogs. Notably, among aged dogs, the levels of Aβ1-42 and the Aβ42/40 ratio were significantly higher in those showing mild cognitive impairment than in either cognitively unimpaired or severely affected dogs. These results suggest that increased plasma Aβ1-42 levels and Aβ42/40 ratio could be a biomarker for canine cognitive dysfunction, which is considered an excellent natural model of early AD. © 2011 Elsevier Inc.

Insua D.,University of Santiago de Compostela | Insua D.,Araclon Biotech Ltd. | Corredoira A.,University of Santiago de Compostela | Gonzalez-Martinez A.,University of Santiago de Compostela | And 4 more authors.
Journal of Alzheimer's Disease | Year: 2012

The canine cognitive dysfunction syndrome (CDS) has been identified as a natural model for Alzheimer's disease (AD). We have used unbiased stereology to estimate the total number of basal forebrain cholinergic neurons expressing the nerve growth factor p75 NTR receptor in young, aged cognitively-unimpaired (CU) and aged cognitively-impaired (CI) dogs. Aged-CI dogs showed a ∼20% decrement (p = 0.009) in p75 NTR neurons compared to both the young and the aged-CU animals. These results suggest that the basal forebrain cholinergic system is affected in dogs with CDS and provide additional support for the use this canine syndrome as a model for AD research. © 2012 - IOS Press and the authors. All rights reserved.

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