Research at the Rodent Behavioural Research Unit:
The Rodent Behavioural Research Unit at the Laboratory of Neurochemistry & Behaviour holds a considerable expertise in the field of behavioural phenotyping of (transgenic) rodent models for human neurological conditions. Behavioural phenotyping is crucially based upon test batteries of behavioural paradigms assessing different brain and behaviour functions. The Research Unit is fully equipped for behavioural observations in rodents (mice and rats), including the evaluation of pharmacological interventions in specific models, as well as correlations between behavioural alterations and underlying disease mechanisms. The behavioural observation ranges from evaluation of simple reflexes to the systematic registration of complex learned responses as studied in the Morris water maze. Besides various levels of learning and memory performance, a test battery may include assessments of motor performance, equilibrium and coordination, circadian rhythms and exploration, anxiety and fear. The research unit has moreover ample experience in behavioural observations related to isolation-induced aggression, male sexual behaviour, depression-related symptoms, vision and olfaction, ingestive behaviour, and epilepsy. In addition, a complete setup for in vivo electrophysiological recordings in rodents is available.
The following research topics are currently under investigation:
- Behavioural phenotyping of transgenic models for Alzheimer's disease and related disorders;
- Pharmacological modulations of cognitive and BPSD-related behavioural alterations in the transgenic APP23 mouse model for Alzheimer's disease;
- Functional peptidomics: study of the behavioural effects of newly discovered peptides.
- Correlation between behavioural deficits and underlying pathophysiological mechanisms in transgenic models for Alzheimer's disease;
Behavioural analyses in rodents using various paradigms employing automated recording systems (Ethovision and custom made) and/or experimenter-based observations;
Acute or chronic administration of compounds
Follow-up breeding colony APP23 mice
Genotyping newborns in breeding colony employing:
- DNA extraction
- agarose gel electrophoresis
Research: Biomarkers for (early) dementia diagnosis
The diagnosis of Alzheimer's disease (AD) is still based on clinical exclusion criteria and the required diagnostic work-up is time consuming and expensive, at best resulting in a diagnosis of probable AD. Average sensitivity and specificity values of respectively 81% and 70% were achieved for a clinical diagnosis of probable AD. Most studies evaluating accuracy rates are, however, based on follow-up periods of several years and have been performed in specialised clinical centres. A much lower diagnostic accuracy can be expected in the earliest stages of the disease and when the diagnostic work-up is performed in non-specialised centres. Low average specificity levels of 48% for clinical diagnosis of possible AD reflect the overlap of clinical profiles between AD and non-AD dementias. Should diagnostic errors occur, they most likely involve one of the other primary dementias, mixed pathologies that include a vascular component, or uncertainties associated with early diagnosis.
A promising approach to increase diagnostic accuracy is the use of biochemical markers (biomarkers) present in easily accessible body fluids like serum, plasma or cerebrospinal fluid (CSF). Within the Reference Centre for Biological Markers of Memory Disorders, we contribute to the development and characterisation of biomarkers, meanwhile developing and validating biomarkers-based diagnostic models that can easily be applied in routine clinical diagnosis. Indeed, several studies have confirmed the relevance of total tau-protein (T-tau) and ß-amyloid peptide (Aß1-42) in the pathogenic processes associated with dementias of neurodegenerative origin. The combined assessment of CSF Aß1-42, T-tau, and tau phosphorylated at threonine 181 (P-tau181P) levels is routinely performed for clinical diagnostic and research purposes.
Recently, we have shown the value of biomarkers in (differential) dementia diagnosis, using the gold standard (pathological diagnosis) as a reference. New models have been developed, enabling the use of the different biomarkers in an optimal algorithm defined by the clinical need. These models show promising sensitivity and specificity. Diagnostic accuracy based on a biomarker model using CSF levels of Aß1-42 and P-tau181P (82.7%) is comparable to diagnostic accuracy strictly applying clinical diagnostic criteria (81.6%), and can help establishing a correct diagnosis in case of doubtful clinical diagnoses. Moreover, biomarkers and biomarker-based diagnostic models are of help for identifying mild cognitive impairment (MCI) patients at risk for conversion to dementia.
- Clinical and behavioural observation of dementia patients