Altmetrics
Downloads
185
Views
108
Comments
0
A peer-reviewed article of this preprint also exists.
supplementary.zip (85.22KB )
Submitted:
21 September 2024
Posted:
24 September 2024
You are already at the latest version
Name of the BBMs | Underlying Pathophysiology |
Current Categorization of BBBMs (NIA-AA'2024) | Relevance in AD | Trend of the biomarker in Plasma | Assessment techniques | |
---|---|---|---|---|---|---|
Amyloid β | Aβ42 | Plasma proteinopathy- Amyloidogenic | Core 1 biomarker (A) |
Early detection of AD in asymptomatic individuals, with progression from normal cognition to MCI or AD | Decreased in AD and MCI in comparison to controls | 1: ELISA 2: Luminex xMAP Technology 3: SIMOA 4: LCMS 5: Immunoprecipitation Mass Spectrometry |
Aβ40 | Plasma proteinopathy- Amyloidogenic | Core 1 biomarker (A) |
Early detection of AD in asymptomatic individuals, with progression from normal conition to MCI or AD | Decreased in AD and MCI in comparison to controls | ||
Aβ42/40 | Plasma proteinopathy- Amyloidogenic | Core 1 biomarker (A) |
Identify early stages of AD and predict cognitive decline in concordance with CSF and neuroimaging biomarkers. | Decreased Aβ42/Aβ40 Ratio in AD and MCI compared to control | ||
Tau | p-tau217 | Plasma proteinopathy-Tauopathy phosphorylated and secreted AD tau | Core 1 biomarker (T1) |
Early detection of AD in people without symptoms -Accurately predict the progression of individuals from subjective cognitive decline (SCD) and MCI to dementia when combined with other risk factors. |
Increased in AD and MCI in compared to controls | 1: ELISA 2: Luminex xMAP Technology 3: SIMOA 4: LCMS 4: Immunoprecipitation Mass Spectrometry |
p-tau181 | Plasma proteinopathy-Tauopathy phosphorylated and secreted AD tau | Core 1 biomarker (T1) |
Early detection of AD in people without symptoms -Distinguishes between Aβ-PET (+) and Aβ-PET (-) individuals, along with the disease progression to dementia and tau-burdened brain areas with AD-related atrophic changes. |
Increased in AD and MCI compared to controls | ||
p-tau 231 | Plasma proteinopathy-Tauopathy phosphorylated and secreted AD tau | Core 1 biomarker (T1) |
-Early detection of AD in people without symptom -Discriminates patients with and without AD pathology during post-mortem assessment. |
Increased in AD and MCI compared to controls | ||
MTBR-tau243 | Plasma proteinopathy-Tauopathy AD tau proteinopathy |
Core 2 biomarker (T2) |
Elevated in later stages of AD Staging of biological disease severity along with Core 1 biomarker -strongly associated with tau-PET and disease progression. |
Increased in AD and MCI compared to controls | ||
Non-phosphorylated mid-region tau fragments |
Plasma proteinopathy-Tauopathy AD tau proteinopathy |
Core 2 biomarker (T2) |
Elevated in later stages of AD -staging of biological disease severity along with Core 1 biomarker. |
Increased in AD and MCI compared to controls | ||
α-synuclein (αSyn) | αSyn/tau | Proteinopathy-related biomarkers of non-core AD pathology Synuclein pathology | Biomarkers of non-AD co-pathology (S) |
Total α-synuclein levels in the blood may not differ significantly between patients with neurodegenerative diseases. The oligomeric or phosphorylated form of α-synuclein accelerates cognitive dysfunction. |
Decreased in AD and MCI compared to controls | 1: Seed Amplification Assays: -Protein Misfolding Cyclic Amplification (PMCA) -Real-Time Quaking-Induced Conversion (RT-QuIC) 2: ELISA and Western blotting 3: Quantitative Mass Spectrometry 4: Luminex xMAP Technology 5: SPR- DLS 6: Immuno-PCR |
αSyn /Aβ 42 | Biomarkers of non-AD co-pathology | Increased in AD and MCI compared to controls | ||||
DKK-1 or Dickkopf-1 | Proteinopathy-related biomarkers of non-core AD pathology. | Research Biomarker | Elevated levels correlate with disease severity, particularly cognitive decline and synaptic loss and help differentiate AD from other neurodegenerative conditions |
Increased in AD | 1: ELISA and Western blotting 2: Luminex xMAP Technology 3: Immuno-PCR 4: Mass Spectrometry |
|
VILIP-1 | Proteinopathy-related biomarkers of non-core AD pathology. | Research Biomarker | Increased levels are seen in AD, but there is no significant difference in concentrations with AD-MCI patients and other neurodegenerative groups. |
Increased in AD | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3. Immuno-PCR 4. Mass Spectrometry |
|
Plasma Neurofilaments (NfL) | Injury, dysfunction, or degeneration of neuropil | Biomarkers of non-specific processes involved in AD pathophysiology (N) |
Increased levels in Aβ-positive patients with AD and MCI are associated with the degree of cognitive impairment as well as used as monitoring biomarkers to indicate the severity of neurodegeneration. | Increased in AD and MCI vs controls | 1. ELISA (Enzyme-Linked Immunosorbent Assay) 2. Luminex xMAP Technology 3. ECLIA 4. Mass Spectrometry 5. SIMOA |
|
SNAP-25 | Neuronal and synaptic injury-pre synaptic dysfunction | Biomarkers of non-specific processes involved in AD pathophysiology (N) |
CSF concentrations can distinguish between various neurodegenerative diseases like AD, Parkinson’s dieases, and ALS. | Decreased in AD compared to controls | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
Neuronal pentraxin 2 (NPTX-2) | Neuronal and synaptic injury-pre synaptic dysfunction | Biomarkers of non-specific processes involved in AD pathophysiology (N) |
Potential as a probable biomarker for early detection of AD. | Decreased in AD compared to control | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
Growth-associated protein (GAP-43) | Neuronal and synaptic injury-pre synaptic dysfunction | Biomarkers of non-specific processes involved in AD pathophysiology (N) |
Potential as a probable biomarker for early detection of AD. | Increased in AD compared to control | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
Neurogranin (NG) | Neuronal and synaptic injury- post-synaptic protein dysfunction | Biomarkers of non-specific processes involved in AD pathophysiology (N) |
Potential as a probable biomarker for early detection of AD. | Decreased in AD compared to control | 1. ELISA 2. Luminex xMAP Technology 3. ECLIA 4. Mass Spectrometry 5. SIMOA |
|
Fms-like tyrosine kinase-1 (Flt-1) | Vascular Damages related to AD | Research Biomarker (V) |
Assess total vascular involvement and early detection of vascular changes associated with AD. |
Increased in AD compared to control | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
Endothelin 1 (ET-1) | Vascular Damages related to AD | Research Biomarker (V) |
Indicates vascular impairment in AD. | Increased in AD compared to AD | 1. ELISA 2. Luminex xMAP Technology 3. Immuno-PCR 4. Mass Spectrometry |
|
Atrial natriuretic peptide (ANP) | Vascular Damage related to AD | Research Biomarker (V) |
Causes reduced cerebral blood flow and impairment of neurovascular health. . |
Increased in AD compared to control | 1. ELISA 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
MIG/CXCL-9 | Vascular Damage related to AD | Research Biomarker (V) |
Indicate ongoing chronic neuroinflammatory processes. | Increased in AD compared to control | 1. ELISA 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
heart-type fatty acid binding protein (H-FABP) | Vascular Damage related to AD | Research Biomarker (V) |
Potential as a probable biomarker for early detection of AD as it was found to be elevated in the pre-clinical phase of AD dementia. | Increased in AD compared to control | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
Vascular adhesion molecular | sVCAM-1 | Vascular Damage related to AD | Research Biomarker (V) |
Indicate the burden of atherosclerosis in AD with elevated sVCAM, indicating a significant correlation between age and the severity of cognitive decline. |
Increased in AD compared to control | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
Soluble intercellular adhesion molecule-1 | Vascular Damage related to AD | Research Biomarker (V) |
Indicate the burden of atherosclerosis in AD with elevated Soluble intercellu-lar adhesion molecule-1. | Increased in AD compared to control | 1. ELISA and Western blotting 2. Luminex xMAP Technology 3.Immuno-PCR 4. Mass Spectrometry |
|
Metabolic products secondary to lipid peroxidation (LPO) | malondialdehyde (MDA) | Oxidative Stress | Research Biomarker | Increased levels in familial AD that carry APP and presenilin-1 gene mutations. | Increased in AD compared to control | 1. HPLC 2. LC-MS 3. ELISA 4. GC-MS |
4-hydroxynonenal (4-HNE) | Oxidative Stress | Research Biomarker | Increased levels in familial AD that carry APP and presenilin-1 gene mutations. | Increased in AD compared to control | ||
increased F2-isoprostanes (F2-IsoPs) | Oxidative Stress | Research Biomarker | potential marker of oxidative stress during the MCI phase of AD, and its quantity correlates with the disease continuum from SCD to MCI to AD. | Increased in AD compared to control | ||
Free radicals | ROS | Oxidative Damage | Research Biomarker | ROS modifies neuronal macromolecules and induces τ protein hyperphosphorylation during prodromal AD phases. | Increased in AD | 1. DCFDA 2. Electron Spin Resonance (ESR) Spectroscopy 3.Nitroblue Tetrazolium (NBT) Assay 4. Flow Cytometry with ROS-sensitive dyes |
RNS | Oxidative damage | Research Biomarker | Nitrosylation of critical proteins in neurons impairs their function, promoting neurodegenerative processes. | Increased in AD | 1. Nitrotyrosine ELISA Electron Spin Resonance (ESR) Spectroscopy Western Blot for 3-Nitrotyrosine-modified Proteins |
|
Nucleoside 8-hydroxyguanosine (8-OHG) | Oxidative Damage | Research Biomarker | It is notable for determining the gradient of DNA oxidative damage in AD patients. It allows us to determine oxidative damage to plasma DNA early in AD. | Increased in lymphocytes of AD patients compared to control | 1. ELISA 2. HPLC and Electrochemical detection 3. LC-MS 4. Western Blot using specific anti-5.8-OHG antibodies 6. Immunoprecipitation 7. GC-MS |
|
Mitochondrial respiratory complex I-V genes (OxPHOS genes) | Bioenergetic abnormality | Research Biomarker | An imbalance in nuclear and mitochondrial genome-encoded OXPHOS transcripts may cause a negative feedback loop that lowers mitochondrial translation and compromises OXPHOS efficiency. This would likely result in the generation of harmful reactive oxygen species. |
Reduced expression in early AD patients | 1. qPCR Western Blot IHC Blue Native Gel Electrophoresis |
|
SNO-Drp1 | Bioenergetic abnormality | Research Biomarker | SNO-Drp1 can result in increased mitochondrial fission, loss of synapses, and neuronal damage in mice models and primary neuronal culture, as well as in post-mortem tissue. | Increased in peripheral blood lymphocytes in AD patients. There are also contradictory findings that SNO-Drp1 does not differ significantly in AD compared to controls. | 1. Biotin Switch Assay Mass Spectrometry Nitroso-Proteome Profiling Immunoprecipitation and Western blot |
|
mitochondrial DNA (mt-DNA) | Bioenergetic abnormality | Research Biomarker | mtDNA copy number acts as an indirect indicator for several functioning mitochondria and thus provides info regarding bioenergetics as a factor for AD progression. | Decreased in patients with AD | 1. qPCR Digital droplet PCR Southern Blotting |
|
8oxoG sSNVs | Bioenergetic abnormality | Research Biomarker | due to their inflammatory endophenotype, the circulating cf-mtDNA (ccf-mtDNA) 8oxoG variant can be used as an improved biomarker. | Increased in AD patients | 1. 8-oxoG DNA Glycosylase (OGG1) Assay Comet Assay with Fpg (Formamidopyrimidine-DNA Glycosylase) ELISA HPLC with electrochemical detection |
|
circulating cf-mtDNA (ccf-mtDNA) | Bioenergetic abnormality | Research Biomarker | cellular mt-DNA copy number can be used as a potential biomarker of mitochondrial biogenesis and cellular energetics to reflect upon mitochondrial health in AD. | Increased in AD patients | qPCR Digital droplet PCR Southern Blotting |
|
The intermediate filament glial fibrillary acidic protein (GFAP) | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
The marker of astrogliosis can be seen in chronic inflammatory processes like progressing AD. | Increases in AD patients | 1. ELISA ECLIA mesoscale discovery immunoassay V-PLEX |
|
CX3CL1 (Fractalkine) | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
significantly elevated in the plasma of MCI and AD compared to other neuroinflammatory disease processes. | Increases in AD and MCI | 1. ELISA Western blot IHC Flow Cytometry Luminex |
|
CCL23 | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
Their plasma concentration has also been found to have a predictive value toward MCI-to-AD progression. | Increases in AD | 1. ELISA Western blot IHC Flow Cytometry Luminex |
|
C-C chemokine ligands or RANTES | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
Elevated in AD and correlate with the neuroinflammatory burden. | Increases in AD | ELISA Western blot IHC Flow Cytometry 5. Luminex |
|
YKL-40 | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
increasingly expressed in astrocytes during neuroinflammatory changes. Plasma YKL-40 level shown to have a positive correlation with the result of sensitive free and cued selective reminding test | Increases in AD | 1. ELISA 2. Western blot 3. IHC 4. Flow Cytometry 5. Luminex |
|
Progranulin | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
Studies have revealed that the increased progranulin-expressing gene GRN is in the blood of MCI and AD patients. | Increases in AD | 1. ELISA 2. Western blot 3. IHC 4. Flow Cytometry 5. Luminex |
|
Triggering receptor expressed on myeloid cells 2 (TREM2) | Neuroinflammation and Immune Dysregulation | Research Biomarker (I) |
mRNA levels in peripheral mononuclear cells have been found to have the distinguishing ability between aMCI, AD, and healthy control individuals and to be dependent on the Apolipoprotein E genotype. | Increases in AD | 1. ELISA 2. Western blot 3. IHC 4. Flow Cytometry 5. Luminex |
|
NDE | P-S396-tau | Tauopathy | Research Biomarker | Can predict the development of AD up to 10 years before the clinical onset of sporadic AD. | Increased in AD | Proteomic Analysis of the EV’s like ELISA |
p-tau 181 | Tauopathy | Research Biomarker | Can predict the development of AD up to 10 years before the clinical onset of sporadic AD | Increased in AD and MCI vs healthy controls | 1 ELISA 2. Ultra-sensitive inhouse SIMOA |
|
Synaptotagmin | Synaptopathy | Research Biomarker | Its impairment leads to decreased neurotransmission, neuroplasticity, and long-term potentiation, thus hampering memory formation. | Reduced in AD | 1. ELISA LC-MS SIMOA |
|
synaptophysin | Synaptic loss and dysfunction | Research Biomarker | Loss of proper functioning synapse leads to impaired signal transmission and, thus, cognitive impairment. | Reduced in AD | 1. ELISA LC-MS SIMOA |
|
P-S312-IRS-1 | Neuroinflammation and Insulin Resistance | Research Biomarker | Its increment promotes insulin resistance, leading to progressive neurodegeneration. | Increased in AD vs. controls | 1. ELISA LC-MS SIMOA |
|
P-panY-IRS-1 | Insulin resistance and Synaptic dysfunction | Research Biomarker | Its reduction promotes insulin resistance, leading to progressive neurodegeneration. | Downregulated in AD | 1. ELISA LC-MS SIMOA |
|
N-(1-carboxymethyl)-L-lysine | ROS mediated damage | Research Biomarker | can differentiate early to moderate AD. | Downregulated in AD | 1. ELISA LC-MS SIMOA |
|
MDE | Tauopathy | Research Biomarker | When neurons absorb microglia-derived exosomes containing tau, it triggers further abnormal tau aggregation | Increases in AD | ELISA LC-MS |
|
ADE | Neuroinflammation | Research Biomarker | Plasma levels of various complement components, such as C1q, C3b, and factor D, could serve as predictive biomarkers for the progression of MCI to AD | Increases in AD | 1. ELISA LC-MS |
Source of the miRNA | Names of miRNA | Reference |
---|---|---|
Whole Blood | hsa-miR-107 | [160,161,162,164] |
Plasma | hsa-miR-92a-3p, hsa-miR-486-5p, hsa-miR-29a-3p, hsa-miR-107, hsa-miR-128-3p, hsa-miR-132-3p, hsa-miR-34c-5p, hsa-let-7d-5p, hsa-miR-191-5p, hsa-miR-200a-3p, hsa-miR-483-5p, hsa-miR-486-5p, hsa-miR-502-3p, hsa-miR-548k, hsa-miR-339-5p, hsa-miR-221-5p, hsa-miR-144-5p, hsa-miR-382-5p, hsa-miR-146b-5p, hsa-miR-224-5p, hsa-miR-625-5p, hsa-miR-769-5p, hsa-miR-454-5p, hsa-miR-548d-5p, hsa-miR-877-5p, hsa-miR-146a, hsa-miR-125b, | |
Serum | hsa-miR-106-b-3p, hsa-miR-22-3p, hsa-miR-126-5p, hsa-miR148b-5p, hsa-miR-181c-3p, hsa-miR-93-5p, hsa-miR-29c-3p, hsa-miR-132-3p, hsa-miR-222-3p, hsa-let-7d-5p, hsa-miR-191-5p, hsa-miR-146a, hsa-miR-125b, hsa-miR-135a | |
PBMC | hsa-miR-128-3p, hsa-miR-34c-5p, |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 MDPI (Basel, Switzerland) unless otherwise stated