COST CM1103 Training School Structure-based drug design for diagnosis and treatment of neurological diseases Istanbul, 9-13 Sept 2013 Mirjana Babić, mag.biol.mol. Laboratory for Developmental Neuropathology Croatian Institute for Brain Research Biomarkers of Alzheimer’s disease
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Mirjana Babić, mag.biol.mol. Laboratory for Developmental Neuropathology
COST CM1103 Training School Structure-based drug design for diagnosis and treatment of neurological diseases Istanbul, 9-13 Sept 2013. Biomarkers of Alzheimer’s disease. Mirjana Babić, mag.biol.mol. Laboratory for Developmental Neuropathology Croatian Institute for Brain Research. - PowerPoint PPT Presentation
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COST CM1103 Training SchoolStructure-based drug design for diagnosis and treatment
of neurological diseasesIstanbul, 9-13 Sept 2013
Mirjana Babić, mag.biol.mol.Laboratory for Developmental Neuropathology
Croatian Institute for Brain Research
Biomarkers of Alzheimer’s disease
“Detection and tracking of biological markers for early therapeutic intervention in sporadic Alzheimer's disease”
Project of the Croatian Science Foundation grant no. 09/16 from 1st Jan 2012 – 31st Dec 2014
• neurodegenerative disorder• loss of memory and cognitive decline• in 2050 - approximately 80 million people will suffer
from Alzheimer’s disease
Alzheimer's disease
Ideal marker for diagnosis of Alzheimer's disease is not found yet!
Diagnosis of AD based on criteria of:• DSM-IV-TR• NINCDS-ADRDA • ICD 10
Characteristics of good marker:• sensitivity and specificity above
85%• availability• non invasiveness• acceptable price • possibility for repetitive measures
Aim of this project• to determine the diagnostic accuracy of potentially highly
useful biological markers for discrimination among subjects mild cognitive impairment (MCI), non-demented HC, and patients with other primary causes of dementia
Neuropsychological testing
• Early detection of non-cognitive BPSD (behavioural and psychological symptoms of dementia):
o NPI (Neuropsychiatric Inventory)o ADAS-noncog (Alzheimer's disease Assessment Scale for non-cognitive
symptoms)o BEHAVE-AD (behaviour rating scale)
Laczo et al., 2009.
• Additional testing of patients with the risk of AD:
o Hidden-goal task (human analogue of the Morris water maze task)
Imaging biomarkers
Earliest change in thebrain of AD patients is atrophy of hippocampus and entorhinal cortex .
4. neuronal development and differentiation (BDNF)
5. lipoproteins’ metabolism (ApoE)
• Specific polymorphisms of genes coding for components of:
CSF biomarkers
• CSF amyloid β1-42, total tau and phosphorylated tau are the main reflect two major neuropathological hallmarks of AD - neurofibrillary tangles and senile plaques.
• T-tau 300% increased in AD patients• Aβ1-42 50% decreased AD
patients
Andreasson et al., 2007.
• Phospho-tau reflects phosphorylation state of tau protein and formation of neurofibrillary tangles in the brain
• Levels of CSF biomarkers vary among different laboratories.• The cause are variations in:1. Pre-analytical procedures 2. analytical procedures 3. differences between ELISA kits of various manufacturers
• Ultimate goal of this project is to predict AD in healthy, asymptomatic subjects