Table 2.
Genes/proteins involved in AD
| Gene symbol | Gene/protein name | Protein function | Reference | Sporadic (s) / familial (f) | Notes |
|---|---|---|---|---|---|
| APP | amyloid beta precursor protein | Precursor of beta amyloid (Aβ) | 53 | f | |
| ABCA7 | ATP binding cassette subfamily A member 7 | Regulates the homeostasis of phospholipids and cholesterol in the CNS | 54 | s | |
| ADAM10 | ADAM metallopeptidase domain 10 | The main α-secretase that cleaves APP in the nonamyloidogenic pathway | 55 | s | |
| ADAMTS4 | ADAM metallopeptidase with thrombospondin type 1 motif 4 | Facilitates Aβ4-x peptide generation | 55 | s | |
| ALPK2 | alpha kinase 2 | Protein serine/threonine kinase activity | 55 | s | |
| APH1B | aph-1 homolog B, gamma-secretase subunit | A functional component of the gamma-secretase complex | 55 | s | |
| APOE | apolipoprotein E | Lipid metabolism | 56 | s | The ε4 allele of APOE is the major genetic risk factor for LOAD |
| ATP5H | ATP synthase peripheral stalk subunit d | ATP biosynthetic process | 57 | s | |
| BIN1 | bridging integrator 1 | Involved in synaptic vesicle endocytosis | 58 | s | |
| CASS4 | Cas scaffold protein family member 4 | It may have a role in axonal transport | 59 | s | |
| CD2AP | CD2 associated protein | Regulates the actin cytoskeleton | 54 | s | |
| CD33 | CD33 molecule | It may have a role in cell-to-cell adhesion | 54 | s | Expressed on cells of myeloid lineage |
| CELF1 | CUGBP Elav-like family member 1 | Involved in pre-mRNA alternative splicing, mRNA translation and stability. | 59 | s | |
| CLNK | cytokine dependent hematopoietic cell linker | Plays a role in the regulation of immunoreceptor signaling | 55 | s | Expressed on cells of myeloid lineage |
| CLU | clusterin | A Golgi chaperone that facilitates the folding of secreted proteins | 60 | s | |
| CNTNAP2 | contactin associated protein like 2 | It may play a role in the local differentiation of the axon | 55 | s | |
| CR1 | complement C3b/C4b receptor 1 (Knops blood group) | Act as a negative regulator of complement cascade, mediating phagocytosis | 61 | s | |
| DRB1 | RNA binding motif protein 45 | Binding to poly(C) RNA | 59 | s | |
| EPHA1 | EPH receptor A1 | Regulates cell proliferation, may play a role in apoptosis | 54 | s | |
| FERMT2 | fermitin family member 2 | Regulates the activation of integrins | 59 | s | |
| HESX1 | HESX homeobox 1 | Involved in forebrain development | 55 | s | |
| INPP5D | inositol polyphosphate-5-phosphatase D | Regulation of cellular activation | 59 | s | |
| KAT8 | lysine acetyltransferase 8 | Selectively inhibits antiviral immunity | 55 | s | |
| MAPT | microtubule associated protein tau | Encodes for tau, the predominant component of neurofibrillary tangles | 62 | f | Unclear Pathogenicity for AD |
| MEF2C | myocyte enhancer factor 2C | Involved in neurogenesis and in the development of cortical architecture | 59 | s | |
| MS4A | membrane-spanning 4A | Participates in the regulation of calcium signaling | 54 | s | |
| NME8 | NME/NM23 family member 8 | Nucleoside diphosphate kinase activity | 59 | s | |
| PICALM | phosphatidylinositol binding clathrin assembly protein | Involved in cellular trafficking and regulation of endocytosis | 60 | s | |
| PLD3 | phospholipase D family member 3 | Involved in APP processing | 63 | s | |
| PSEN1 | presenilin 1 | Part of the γ-secretase complex, regulating APP processing | 64 | f | |
| PSEN2 | presenilin 2 | Part of the γ-secretase complex, regulating APP processing | 65 | f | |
| PTK2B | protein tyrosine kinase 2 beta | Enhances signals that regulate neuronal activity | 59 | s | |
| RIN3 | Ras and Rab interactor 3 | Involved in the early endocytic pathway | 59 | s | |
| SORL1 | sortilin related receptor 1 | A neuronal apolipoprotein E receptor | 59 | s | |
| TREM2 | triggering receptor expressed on myeloid cells 2 | Phagocytosis, migration, activation | 66 | s | Exclusively expressed on cells within the myeloid lineage. SNPs increase disease risk by 2- to 4-fold. |
| TRIP4 | thyroid hormone receptor interactor 4 | Paly a role in the estrogen receptor and NF-κB transactivation | 67 | s | |
| UNC5C | unc-5 netrin receptor C | Direct axon extension and cell migration during neural development | 68 | s | |
| ZCWPW1 | zinc finger CW-type and PWWP domain containing 1 | A histone modification reader involved in epigenetic regulation | 59 | s |
Abbreviations: AD, Alzheimer’s disease; APP, amyloid precursor protein, Aβ, amyloid beta, ATP, adenosine triphosphate; CNS, central nervous system; APOE, apolipoprotein E, mRNA, messenger RNA; NF-κB, nuclear factor kappa B; RNA, ribonucleic acid.