Genes associated with Alzheimer’s disease: an overview and current status

Figures & data

Table 1 Genes implicated in risk of early-onset Alzheimer’s disease

Gene symbol	Location	Function	Pathway	References
APP	21q21.3	Neuronal development, Synaptic formation and repair, β-Amyloid production	APP processing	^Citation13^–^Citation15,Citation18
PSEN1	14q24.3	γ-Secretase activity, Intracellular signaling, β-Amyloid production	APP processing	^Citation9,Citation26,Citation27
PSEN2	lq42.13	γ-Secretase activity, β-Amyloid production, Synaptic plasticity	APP processing	^Citation13,Citation27,Citation36

Figure 1 Major pathways involved in AD and affected genes.

Abbreviation: AD, Alzheimer’s disease.

Table 2 Common and rare variants associated with Alzheimer’s disease

Gene	Chromosome	SNP	Function	Pathway	References
APOE	19q13.2		Lipid transport Synaptic vesicle endocytosis Cytoskeletal dynamics	Lipid metabolism	^Citation41^–^Citation44
CLU	8p21-p12	rs11136000	Synapse turnover Complement regulation Chaperone protein	Cholesterol metabolism and immune response	^Citation37,Citation66,Citation67
ABCA7	9p13.3	rs3764650 rs3752246	Phagocytosis Lipid homeostasis	Lipid metabolism Immune response	^Citation72,Citation74,Citation78
SORL1	11q23.2-q24.2	rs12285364	Endocytosis Receptor for APOE Processing of APP	Endocytosis Lipid metabolism	^Citation79,Citation81,Citation88
CR1	1q32	rs3818361 rs6656401	Amyloid β clearance Complement activation	Immune response	^Citation91,Citation92,Citation94
CD33	19q13.3	rs3865444 rs3826656	Clathrin-mediated endocytosis Cell signaling	Immune response	^Citation97,Citation101
MS4A	11q12.2	rs610932 rs670139 rs4938933	Signal transduction Immune function	Immune response	^Citation102,Citation103
TREM2	6p21.1	rs75932628	Inflammatory response	Immune response	^Citation104,Citation107,Citation110
BIN1	2q14.3	rs744373 rs7561528	Synaptic vesicle endocytosis APP trafficking Cytoskeletal dynamics	Synaptic vesicle endocytosis	^Citation114,Citation118
CD2AP	6p12	rs9296559 rs9349407	Receptor-mediated endocytosis Cytokinesis Cytoskeletal dynamics	Endocytosis Synapse function	^Citation119,Citation120,Citation122
PICALM	11q14	rs3851179 rs541458	Clathrin-mediated endocytosis	Endocytosis Synapse function	^Citation114,Citation123,Citation125
EPHA1	7q34	rs11771145 rs11767557	Synaptic development Immune function Neural development	Immune response	^Citation38,Citation132,Citation133
HLA-DRB5/HLA-DRB1	6p21.3	rs9271192	Immune function Histocompatibility	Immune response	^Citation38,Citation135,Citation137
INPP5D	2q37.1	rs35349669	Cytokine signaling Immune function	Immune response	^Citation38,Citation138
MEF2C	5q14.3	rs190982	Myogenesis Synapse formation	Immune response Hippocampal synaptic function	^Citation140,Citation141
CASS4	20q13.31	rs7274581 rs6024870 rs16979934	Cell migration Cell adhesion	Cytoskeletal function and axonal transport	^Citation134,Citation142,Citation144
PTK2B	8p21.1	rs28834970	Calcium homeostasis MAP kinase signaling	Hippocampal synaptic function	^Citation146,Citation147
NME8	7p14.1	rs2718058	Ciliary function Neuronal cell proliferation	Axonal transport and cytoskeletal function	^Citation149,Citation150
ZCWPW1	7q22.1	rs1476679	Epigenetic regulation Neural development	Epigenetic regulation	^Citation153,Citation154
CELF1	11p11	rs10838725	mRNA editing Pre-mRNA splicing	Cytoskeletal function and axonal transport	^Citation144,Citation155
FERMT2	14q22.1	rs17125944	Cell–cell adhesion Angiogenesis	Tau pathology Angiogenesis	^Citation134,Citation160
SLC24A4/RIN3	14q32.12	rs10498633	Cell signaling Neural development	Synapse function endocytosis	^Citation166,Citation169
DSG2	18q12.1	rs8093731	Cell–cell adhesion		^Citation38,Citation172,Citation173
PLD3	19q13.2	rs145999145	Signal transduction Epigenetic modification	Lipid metabolism	^Citation174,Citation175
UNC5C	4q22.3	rs137875858	Neural development		^Citation177
AKAP9	7q21-q22	rs144662445 rs149979685	Signal transduction		^Citation183,Citation184
ADAM10	15q22	rs2305421	Hippocampal neurogenesis Cell adhesion		^Citation186,Citation187

Abbreviation: SNP, single-nucleotide polymorphism.

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