11193549
Biomarkers in Alzheimer's Disease Analysis
by Mass Spectometry- Based Proteomics
- BIOMARKER: substance used as measurable indicator of a
particular biological state (normal or pathologic)
- IT SHOULD REFLECT: progression of disease
providing better prognosis and early
diagnosis
- based on mass specrometry proteomics
(whose goal is to identify and quantify
proteins from biological samples)
- SOURCES: human samples (fluids: blood,
CSF, urine and saliva. DNA (and
modifications), RNA, miRNA, proteins
(PTM)
- SOURCES: human samples (fluids: blood,
CSF, urine and saliva. DNA (and
modifications), RNA, miRNA, proteins
(PTM)
- based on mass specrometry proteomics
(whose goal is to identify and quantify
proteins from biological samples)
- 3 PHASES IN THE
DEVELOPMENT OF A NEW ONE
- DISCOVERY PHASE: proteomic
techniques are applied to blood or
CSF to identify candidates
- VERIFICATION PHASE: quantify the
candidates to confirm differential
expression in blood/CSF from cases
vs controls
- VALIDATION PHASE: considered for
further clinical evaluation
- MRM-MS and
immunoassay
- MRM-MS and
immunoassay
- MRM-LC-MS/MS
- VALIDATION PHASE: considered for
further clinical evaluation
- LC-MS/MS with
fractionation
- VERIFICATION PHASE: quantify the
candidates to confirm differential
expression in blood/CSF from cases
vs controls
- DISCOVERY PHASE: proteomic
techniques are applied to blood or
CSF to identify candidates
- TYPES
- DNA- BASED
- BLOOD- BASED:
- CSF- BASED
- PROTEINS: 0.15-0.45 g/L in plasma,
proximal to the CNS (interacts with
brain, reflects its biochemical
changes), highly invasive, contáis
components form the blood and
CNS
- MS, microarray, 2D gel
- changes at
protein levels
are associated
with AD
- basic biomarker:
albumin (biomarker
for blood brain
barrier BBB)
- increase=
BBB damage
- increase=
BBB damage
- sPLA2 is a BBB factor
- increase=
BBB damage
- increase=
BBB damage
- Visinin-like 1 increased after stroke
- increase in tau/pTau= MCI to AD
- increase in neurofilament proteins= neuronal damage
- downgrade in FAB3, CHGA, B, Neurogranin
- elevated S-100B, GFAP
- related to Aβ
- BACE1, sAPPα/sAPPβ, or Aβ oligomers
- BACE1, sAPPα/sAPPβ, or Aβ oligomers
- basic biomarker:
albumin (biomarker
for blood brain
barrier BBB)
- changes at
protein levels
are associated
with AD
- MS, microarray, 2D gel
- PROTEINS: 0.15-0.45 g/L in plasma,
proximal to the CNS (interacts with
brain, reflects its biochemical
changes), highly invasive, contáis
components form the blood and
CNS
- PROTEINS: 60-80 g/L in plasma,
blood is in contact with all cells,
easily accesible (non-invasive),
cost-time efficient, can be
separated into components
(plasma and serum)
- MS, microarray, 2D gel
- changes at
protein levels
are associated
with AD
- downregulated Aβ (plasma biomarker)
- upregulated ApoE (chromosome 19)
- IL-1α, IL-6 (increase risk)
- Clusterin: ilipoprotein that is part of amyloid plaques
- increased α-1-antichymotrypsin: inflammatory
cascade and formation od amyloid fibrils
- downregulated ADNP in early phase
- downregulated Aβ (plasma biomarker)
- changes at
protein levels
are associated
with AD
- MS, microarray, 2D gel
- CSF- BASED
- DNA methylation studies.
Obtained from cells and
exosomes in plasma
- miRNA: non-coding, players of
postranscriptional gene
modification
- DETECTED BY: RT-PCR,
microarray and
sequencing, 2D gel
- changes at
miRNA levels
are associated
with AD
- upregulation:
miR-9,-125,-128, -34a,
-145b, -155
- downregulation: miR-107,
-137, -181c, -9, -29b,
-146a
- upregulation:
miR-9,-125,-128, -34a,
-145b, -155
- changes at
miRNA levels
are associated
with AD
- DETECTED BY: RT-PCR,
microarray and
sequencing, 2D gel
- BLOOD- BASED:
- DNA- BASED
- PROTEOMIC TECNIQUES
- they include several components: sample
preparation, primary separation, protein
or peptide identification and bioinformatic
data analysis.
- 2D GEL
- LC-mass spectometry
- clinical testing
- radioimmunoassays
- Western-blott
- ELISA
- MRM-Mass spectrometry
- 2D GEL
- they include several components: sample
preparation, primary separation, protein
or peptide identification and bioinformatic
data analysis.
- IT SHOULD REFLECT: progression of disease
providing better prognosis and early
diagnosis
- ALZHEIMER'S DISEASE (AD) develops slowly from 1)
preclinical phase to 2) clinical syndrome
- BIOMARKERS CURRENLY
USED: primary (Aβ and tau)
- possible biomarkers
- BIOMARKERS CURRENLY
USED: primary (Aβ and tau)
- TAREA 09 ARRIOLA VÁZQUEZ
MARÍA JOSÉ, GARCÍA
ECHEVERRIA GALA, JIMENEZ
DELGADO ZOHE MUÑOZ-LEDO
CERON PAULINA,
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