Table 1.
Summary of the main AD fluid biomarkers.
| Change in AD versus
controls |
|||
|---|---|---|---|
| Pathological mechanism | Biomarker | CSF | Serum/plasma |
| Aβ pathology | Aβ42 or Aβ42/40 | ↓ | ↓ |
| BACE1 | ≈ | ↑ | |
| sAPPα and sAPPβ | ≈ | ○ | |
| Tau pathology | t-tau | ↑ | ↑ |
| p-tau | ↑ | ↑ | |
| Neuronal injury | NfL | ↑ | ↑ |
| VILIP-1 | ↑ | ↑ | |
| Synaptic dysfunction | Neurogranin | ↑ | = |
| GAP-43 | ↑ | ○ | |
| Synaptotagmin-1 | ↑ | ↓ | |
| SNAP-25 | ↑ | ○ | |
| Vascular dysregulation | CSF/serum albumin ratio | NA | ↑ |
| VCAM1/ICAM1 | ↑ | ↑ | |
| sPDGFR-β | ○ | ○ | |
| Inflammation | sTREM2 | ↑ | = |
| Progranulin | ≈ | ≈ | |
| YKL-40 | ≈ | = | |
| IP-10 | ≈ | ≈ | |
| GFAP | ≈ | ↑ | |
| MCP-1 | = | ≈ | |
| TDP-43 pathology | TDP-43 | ≈ | ↑ |
| α–synuclein pathology | α-synuclein | ≈ | = |
Overview of the main AD-related fluid biomarkers. The table depicts the changes observed in AD (prodromal, dementia, or both) compared with controls as follows: ↑ increased or ↓ decreased levels in most or all studies; = no changes; ≈ inconsistent results; ○ unknown; NA not applicable. To complete these table, we reviewed all studies available in AlzBiomarker (https://www.alzforum.org/alzbiomarker) for GFAP, MCP-1, neurogranin, NfL, sAPPα, sAPPβ, sTREM2, VILIP-1, YKL-40. For Aβ, t-tau, and p-tau we reviewed those studies in AlzBiomarker with a total number of patients >300. We also included other biomarkers not available in AlzBiomarker that we, however, found relevant for AD.
Aβ, β-amyloid; BACE1, β-site amyloid precursor protein cleavage enzyme 1; CSF, cerebrospinal fluid; GAP-43, Growth-associated protein 43; GFAP, Glial fibrillary acidic protein; ICAM-1, intercellular adhesion molecule-1; IP-10, interferon-inducible protein-10; MCP-1, Monocyte chemoattractant protein-1; NA, not applicable; NfL, neurofilament light; p-tau, phosphorylated tau; sAPP, soluble N-terminal fragment of APP; SNAP-25, synaptosome-associated protein 25; sPDGFR-β, soluble platelet-derived growth factor receptor-β; sTREM2, soluble triggering receptor expressed on myeloid cells 2; TDP-43, transactive response DNA-binding protein 43; t-tau, total tau; VCAM-1, vascular cell adhesion molecule-1; VILIP-1, visinin-like protein 1; YKL-40, chitinase 3-like protein 1.