Supplementary text S2. List of genes used for exome sequencing in the study. The list of genes was taken from AlzGene database (ref. 6). Descriptions according to GenBank database are provided. Mentions of Alzheimer disease are highlighted.

  1. A2M (CPAMD5; FWP007), alpha-2-macroglobulin (12p13.3-p12.3)

[Alpha-2-macroglobulin is a protease inhibitor and cytokine transporter. It inhibits many proteases, including trypsin, thrombin and collagenase. A2M is implicated in Alzheimer disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits.]

  1. ABCA1, ATP-binding cassette, sub-family A (ABC1), member 1 (9q31.1)

[The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes.Intronic polymorphism of ABCA1 gene is associated with sporadic Alzheimer's disease.]

  1. ABCA12 (LI2; ICR2B; FLJ41584; DKFZp434G232), ATP-binding cassette, sub-family A (ABC1), member 12 (2q34)

[The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. Two common polymorphisms of the ABCA12 gene, rs952718 (T/G) and rs956133 (A/G), showed no association with the risk of AD.]

  1. ABCB1 (CLCS; MDR1; P-GP; PGY1), ATP-binding cassette, sub-family B (MDR/TAP), member 1 (7q21.12)

[The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes.Results indicate that Creutzfeldt-Jakob disease, like Alzheimer's disease, is associated with a decrease in the expression of cerebrovascular P-glycoprotein.]

  1. ABCG1 (ABC8; WHITE1; MGC34313), ATP-binding cassette, sub-family G (WHITE), member 1, (21q22.3)

[The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. Altered cholesterol metabolism and amyloid precursor protein trafficking mediated by ABCG1 may contribute to the accelerated onset of Alzheimer's disease neuropathology in Down syndrome.]

  1. ACAD8 (ARC42; ACAD-8; FLJ22590), acyl-Coenzyme A dehydrogenase family, member 8 (11q25)

[This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids.The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P < or = 0.05 in this sample.]

  1. ACAT1 (T2; MAT; ACAT; THIL), acetyl-Coenzyme A acetyltransferase 1 (11q22.3-q23.1)

[This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA.Genes studied encompass both novel candidates as well as several recently claimed to be associated with AD (e.g. urokinase plasminogen activator (PLAU) and acetyl-coenzyme A acetyltransferase 1 (ACAT1)).

  1. ACE, angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (17q23.3)

[This gene encodes an enzyme involved in catalyzing the conversion of angiotensin I into a physiologically active peptide angiotensin II. This enzyme plays a key role in the renin-angiotensin system.ACE as a susceptibility locus for Alzheimer disease.The observed reduction in plasma ACE in Alzheimer disease may reflect a general decrease in the zinc metalloprotease-mediated shedding of a subset of membrane-bound proteins.]

  1. ACHE (YT; ARACHE; N-ACHE), acetylcholinesterase (Yt blood group) (7q22)

[Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen.A significant association for Alzheimer disease was detected for a non-coding polymorphism in ChAT (allele chi(1) (2) = 12.84, P = 0.0003; genotype chi(2) (2) = 11.89, P = 0.0026).]

  1. ADAM9, cellular disintegrin precursor (chromosome:15)

[A disintegrin and metalloproteinase (ADAM) 9 can cleave the amyloid precursor protein (APP) within the Abeta domain and preclude generation of Abeta peptides.data suggest that promoter polymorphisms which regulate ADAM9 transcription are protective against SAD.]

  1. ADAM10(a member of a disintegrin and metalloprotease family); (15q2; 15q22)

[Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity]

  1. ADAM12 (MCMP; MLTN; MLTNA; MCMPMltna), ADAM metallopeptidase domain 12 (10q26.3)

[This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins. A recent study reported a statistically significant interaction between 2 variants of these genes (rs3740473 for SH3PXD2A and rs11244787 for ADAM12) with respect to the risk of developing AD.

  1. ADRB1 (RHR; B1AR; ADRB1R; BETA1AR), adrenergic, beta-1-, receptor (10q24-q26)

[The adrenergic receptors (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. Data strongly indicate that the combination of GNB3 and ADRB1 polymorphisms produces AD susceptibility by changing the cell responsiveness to adrenergic stimulation, pointing to the modulation of brain adrenergic receptors as a potential target for novel AD therapeutic strategies.]

  1. AGER (RAGE), advanced glycosylation end product-specific receptor (6p21.3)

[This gene encodes a member of the immunoglobulin superfamily of cell surface molecules. It is a receptor for various molecules, including the amyloidogenic form of serum amyloid A, amyloid-beta protein, members of the S100/calgranulin superfamily and advanced glycation end products.The up-regulation of RAGE in the Alzheimer Disease optic nerves indicates that RAGE may play a role in the pathophysiology of Alzheimer Disease optic neuropathy.]

  1. AHSG (AHS; A2HS; HSGA; FETUA), alpha-2-HS-glycoprotein (3q27)

[Alpha2-HS glycoprotein (AHSG), a glycoprotein present in the serum, is synthesized by hepatocytes. The AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. The results suggest that the AHSG gene polymorphism may be associated with LOAD in Italians.]

  1. ALDH2 (ALDM; ALDHI; ALDH-E2), aldehyde dehydrogenase 2 family (mitochondrial) (12q24.2)

[This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism.A case-control study from Japan found that ALDH2*2 was associated with late-onset AD (LOAD). These results suggested that the ALDH2 gene 1/2 polymorphism might be a risk factor for LOAD and dependent on APOE epsilon4 status in Chinese.]

  1. ANK3,ankyrin 3, node of Ranvier (ankyrin G), (10q21)

[Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains.Significant association with late-onset Alzheimer's disease for 4 SNPs: rs1881747 near DKK1, rs2279420 in ANK3, rs2306402 in CTNNA3, and rs5030882 in CXXC6 in 1,160 cases and 1,389 controls.]

  1. APBB1,amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65), (11p15)

[The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription.]

  1. APOA1 (MGC117399), apolipoprotein A-I (11q23-q24)

[This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. These results suggest that variants of APOA1 might influence the onset and the risk for AD.]

  1. APOA4 (MGC142154; MGC142156), apolipoprotein A-IV (11q23)

[Apoliprotein (apo) A-IV gene contains 3 exons separated by two introns. A sequence polymorphism has been identified in the 3'UTR of the third exon. A cluster of polymorphisms in APOE, SOAT1, APOE 5'-untranslated region, OLR1, CYP46A1, LPL, LIPA, and APOA4 conferring significant (p = .0002) susceptibility for Alzheimer's disease.]

  1. APOC1, apolipoprotein C-I; (19q13.2)

[APOC1 might be an additional susceptibility gene for late onset Alzheimer disease]

  1. APOC3 (APOCIII; MGC150353), apolipoprotein C-III (11q23.1-q23.2)

[Apolipoprotein C-III is a very low density lipoprotein (VLDL) protein. APOC3 inhibits lipoprotein lipase and hepatic lipase. he rare APOC3 G allele may offer some protection against the development of sporadic AD in APOE epsilon4 noncarriers in Chinese.]

  1. APOD, apolipoprotein D (3q26.2-qter)

[This gene encodes a component of high density lipoprotein that has no marked similarity to other apolipoprotein sequences.Case-control analysis revealed that the rs5952T-rs1568566C haplotype could serve as a novel defendant factor against SAD. APOD polymorphisms might play an important role in modifying SAD risk in some way.]

  1. APOE (19q13.2)[Alzheimer disease 4]
  2. APP,amyloid beta-protein precursor gene, A4;(21q11.2-q21)[Alzheimer disease 4]
  3. AQP1 (CO; CHIP28; AQP-CHIP; MGC26324), aquaporin 1 (Colton blood group) (7p14)

[Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). This gene encodes an aquaporin which functions as a molecular water channel protein. Observations suggest the possible association of astrocytic AQP1 with Abeta deposition in Alzheimer disease brains.]

  1. ARMS2 (ARMD8), age-related maculopathy susceptibility 2 (10q26.13)

[This gene encodes a protein that is thought to play a role in diseases in the elderly. Mutations in this gene have been associated with age-related macular degeneration.The LOC387715/ARMS2 gene is expressed in the human brain, and it may concur to the individual risk for AD. ]

  1. ARSB, arylsulfatase B, (5q11-q13)

[Arylsulfatase B encoded by this gene belongs to the sulfatase family. The arylsulfatase B homodimer hydrolyzes sulfate groups of N-Acetyl-D-galactosamine, chondriotin sulfate, and dermatan sulfate. The protein is targetted to the lysozyme. Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. (Novel susceptibility genes for Alzheimer's disease)]

  1. ATP2C1 (HHD; BCPM; PMR1; SPCA1; hSPCA1; ATP2C1A; KIAA1347), ATPase, Ca++ transporting, type 2C, member 1 (3q22.1)

[The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.Data show that the calcium dependencies of intracellular Ca(2+)-ATPase (SERCA and SPCA) activity are the same in human Alzheimer disease and normal brain but that of plasma membrane Ca(2+)-ATPase (PMCA) is different.]

  1. BACE1, beta-site APP-cleaving enzyme 1 (11q23.2-q23.3)

[Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease. Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein (APP) by two proteases, one of which is the protein encoded by this gene.It plays a role in membrane protein shedding and produces amyloid beta proteins, which accumulation in central nervous system causes Alzheimer disease].

  1. BAT1, HLA-B associated transcript 1, (6p21.3)

[This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and also plays an important role in mRNA export from the nucleus to the cytoplasm. A cluster of genes, BAT1-BAT5, is localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. APOE epsilon4 was associated with an independent increase in risk for Alzheimer's disease (AD) in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE epsilon4 genotype.]

  1. BCHE (E1; CHE1), butyrylcholinesterase (3q26.1-q26.2)

[Mutant alleles at the BCHE locus are responsible for suxamethonium sensitivity. Homozygous persons sustain prolonged apnea after administration of the muscle relaxant suxamethonium in connection with surgical anesthesia.BuChE genotype may have a role in progression from mild cognitive impairment to Alzheimer's disease.]

  1. BDNF (MGC34632), brain-derived neurotrophic factor (11p13)

[The protein encoded by this gene is a member of the nerve growth factor family. It is induced by cortical neurons, and is necessary for survival of striatal neurons in the brain. Expression of this gene is reduced in both Alzheimer's and Huntington disease patients.]

  1. BECN1,beclin 1 (autophagy related); (17q21)
  2. BRCA1, breast cancer 1, early onset (17q21)

[This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor.Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers.BRCA1 was present in brain tissue of all cases of Alzheimer disease.]

  1. CAND1 (TIP120; TIP120A; FLJ10114),cullin-associated and neddylation-dissociated 1, (12q14)

[(Novel susceptibility genes for Alzheimer's disease)]

  1. CACNB2 (MYSB; CAVB2; CACNLB2; FLJ23743), calcium channel, voltage-dependent, beta 2 subunit (10p12)

[This gene encodes a subunit of a voltage-dependent calcium channel protein which is a member of the voltage-gated calcium channel superfamily.CACNB2 SNPs show genotypic association with Alzheimer disease.]

  1. CARD8 (NDPP; DACAR; TUCAN; CARDINAL; FLJ18119; FLJ18121; KIA), caspase recruitment domain family, member 8 (19q13.33)

[The protein encoded by this gene belongs to the caspase recruitment domain (CARD)-containing family of proteins, which are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NFKB).Gene-gene interaction between CARD8 and interleukin-6 reduces Alzheimer's disease risk.]

  1. CASR (CAR; FHH; FIH; HHC; EIG8), calcium-sensing receptor (3q13)

[The protein encoded by this gene is a G protein-coupled receptor that is expressed in the parathyroid hormone (PTH)-producing chief cells of the parathyroid gland, and the cells lining the kidney tubule.CASR has a role in Alzheimer disease susceptibility.]

  1. CAV1 (CGL3; BSCL3; VIP21; MSTP085), caveolin 1, caveolae protein, 22kDa (7q31.1)

[The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN. We report a novel polymorphic purine complex stretching approximately 150 bp of genomic DNA at the 1.5 kb upstream region of the human CAV1 gene, alleles and genotypes of which are associated with sporadic late-onset Alzheimer's disease.]

  1. CBS (HIP4), cystathionine-beta-synthase (21q22.3)

[The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine, the first step in the transsulfuration pathway.844ins68 mutation and VNTR allele 19 are independent risk factors for Alzheimer disease development in subjects aged 75 years or more.]

  1. CD14, CD14 molecule (5q22-q32; 5q31.1)

[CD14 is a surface protein preferentially expressed on monocytes/macrophages. It binds lipopolysaccharide binding protein and recently has been shown to bind apoptotic cells. Microglia-derived soluble CD14 is a candidate CSF biomarker for Alzheimer's and Parkinson's disease.]

  1. CD36 (FAT; GP4; GP3B; GPIV; CHDS7; PASIV; SCARB3), CD36 molecule (thrombospondin receptor) (7q11.2)

[The protein encoded by this gene is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin in platelets and various cell lines. 5 genes (POU2F1, MYH8, CD36, DPYS, COL11A1)showed a significant association with AD.]

  1. CD40, CD40 molecule, TNF receptor superfamily member 5; (20q12-q13.2)

[The protein encoded by this gene is a member of the TNF-receptor superfamily. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis.]

  1. CDK1 (CDC2; CDC28A; P34CDC2; MGC111195), cyclin-dependent kinase 1 (10q21.1)

[The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This study suggests that the I-G-T haplotype of the CDC2 gene increases the risk of AD in APOE epsilon4 carriers.]

  1. CDK5 (PSSALRE), cyclin-dependent kinase 5 (7q36)

[Variations in the CDK5 gene can be described in 5 haplotype blocks. In our analysis, the haplotype tagged by the G allele of SNP rs2069442 was significantly associated with AD (p = 0.05).]

  1. CDK5R1 (p23; p25; p35; NCK5A; CDK5P35; MGC33831), cyclin-dependent kinase 5, regulatory subunit 1 (p35) (17q11.2)

[The protein encoded by this gene (p35) is a neuron-specific activator of cyclin-dependent kinase 5 (CDK5); the activation of CDK5 is required for proper development of the central nervous system. Subjects carrying both the CDK5R1 (3'-UTR, rs735555) AA genotype and the GSK-3beta (-50, rs334558) CC genotype had a 12.5-fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01-0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.]

  1. CDKN2A (ARF; MLM; p14; p16; p19;), cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (9p21)

[This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported. CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p.]

  1. CETP, cholesteryl ester transfer protein, plasma (16q21)

[Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters between lipoproteins. CETP may effect susceptibility to atherosclerosis.CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.]

  1. CFH (FH; HF; HUS; FHL1; AHUS1; ARMD4; ARMS1), complement factor H (1q32)

[This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short concensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections.The CFH 1277C allele may predispose patients for co-morbidity in Alzheimer disease and age-related macular degeneration.]

  1. CHAT, choline acetyltransferase (10q11.2)

[This gene encodes an enzyme which catalyzes the biosynthesis of the neurotransmitter acetylcholine. This gene product is a characteristic feature of cholinergic neurons, and changes in these neurons may explain some of the symptoms of Alzheimer disease.]

  1. CHMP2B, chromatin modifying protein 2B (3p11.2)

[This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. A mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of family with autosomal dominant frontotermporal dementia.]

  1. CHRFAM7A (D-10; CHRNA7; MGC120482; MGC120483), CHRNA7 (cholinergic receptor, nicotinic, alpha 7, exons 5-10) and FAM7A (family with sequence similarity 7A, exons A-E) fusion (15q13.1)

[The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The family member CHRNA7, which is located on chromosome 15 in a region associated with several neuropsychiatric disorders. The -2 bp polymorphism of CHRFAM7A can be implicated in AD, DLB and PiD. ]