Table 3 Agreement of AD specific LC–ESI–MS/MS results with previous genetic, genomic and biochemical experiments from an automated search of NCBI PubMed

APC

Anaphase-promoting complex

The anaphase-promoting complex (APC) pathway was shown to regulate dendritic memory

[132]

APOE

Lipid binding and transport

Carboxyl-terminal-truncated Apolipoprotein E4 causes Neurodegeneration in mice

[94]

BAG1

BCL2 Associated Athanogene

Is associated with memory deficit in Alzheimer’s

[33, 34]

BRCA1

RING-Type E3 Ubiquitin Transferase

May have a role in neuron death in Alzheimer’s

[133]

C1Q & C9

Complement activation

Upregulation complement C1Q and C9 in AD

[134]

CDC27

APC component catalyzes the formation of cyclin B-ubiquitin conjugate

Knockdown of CDC27 leads to enhanced neurite growth

[135]

CDH13

calcium-dependent cell adhesion protein cadherin 13

Was implicated in Alzheimer’s

[136]

CHD9

Chromodomain Helicase DNA Binding Protein 9

Is closely related to a brain specific DNA remodelling enzyme

[137]

CUX

CUX1

Cut Like Homeobox

Repressor of dendrite morphology and arborisation

[138]

[138]

DAPK

The cell death-associated protein kinase family

May be therapeutic targets in AD

[98]

DISC1

Disrupted in Schizophrenia 1

Coiled-coil and leucine zippers that may mediate protein–protein interactions

[44, 46, 87, 126, 130]

EXOC3L4

Variants in the splicing regulatory elements?

Were associated with Alzheimer’s disease

[99]

FUT9

Fucosyltransferase IX

Amyloid β-peptide 1–42 modulates the expression activity

[139]

GALNT7

Acetylgalactosaminyltransferase 7, related to GALNT3

Genomic sequence data has related, with Alzheimer’s disease

[140]

GRID2

Glutamate Ionotropic Receptor Delta Type Subunit 2

Is important for the function of the NMDA receptor that is a therapeutic target in AD

[100]

GRXCR1

Glutaredoxin And Cysteine Rich Domain Containing 1

Was observed in the plasma of AD patients and Glutaredoxin was released to the cerebrospinal fluid in the early stages of AD

[101]

HACD1

Protein Tyrosine Phosphatase-Like (PTPLA) now referred to as 3-Hydroxyacyl-CoA Dehydratase 1

Genomic methods have indicated that HACD1 plays a role in AD

[141]

HMGA1

High Mobility Group AT-Hook 1

Induces aberrant exon skipping of Presenilin-2 (PS2) RNA, in sporadic Alzheimer’s disease

[93]

HSP90

Human Hsp90

May form a toxic complex with Tau in AD

[142]

ILK

Integrin-linked Kinase

Expression rescued hippocampal neurogenesis and memory deficits in an AD animal model

[143]

KIF12

Brain specific protein Kinesin

Play a role in cellular transport and secretion,

[89, 114, 144]

KIR222 KIR3DP1

Killer inhibitory receptors

Killer inhibitory receptors similar to KIR222 and KIR3DP1 were associated with Alzheimer’s disease

[102, 103]

L3MBTL2

Genomic variants of Histone Methyl-Lysine Binding Protein 2

Were significantly associated with AD

[105]

MAP3K19

Dual Leucine Zipper-Bearing Kinases similar to Mitogen-Activated Protein Kinase Kinase Kinases (MAPKKK)

May play a role in Neuronal Development and Stress Management

[145]

METTL17

Methyltransferases

The inhibition of methyltransferases rescued synaptic and cognitive functions for Alzheimer’s disease

[106]

NET1

RHOGEF Neuroepithelial cell-transforming 1

Is involved in cell proliferation in neurological development

[107]

NEUROG2

Basic helix-loop-helix (bHLH) transcription factor Neurogenin 2

Plays a role in the development of Neurons via the Wnt/β-Catenin pathway

[108]

NGF

Nerve Growth Factor

Nerve growth factor governs the development of neurons

[4]

NOX1

NADPH Oxidase

May play a role in neurodegenerative disorders

[146]

NPR2

Natriuretic Peptide Receptor 2

Internalization of amyloid-β sensitive to natriuretic peptides

[109, 110]

NT5C3A

5'-Nucleotidase

May be expressed in the early stages of Alzheimer’s disease

[147]

NUP210

Nucleoporin 210

The gene is active specifically in the prefrontal cortex neurons

[148]

NXNL1

Rod-Derived Cone Viability Factor Nucleoredoxin Like 1

Loss of optical sensory nerve cells in retinitis pigmenstosa

[97]

NXNL1

Nucleoredoxin Like 1

TAU phosphorylation is increased in NXNL1 (−/−) mice

[95]

OGFOD3

2-Oxoglutarate-dependent Dioxygenases

Sense energy metabolism, oxygen and iron homeostasis that might have a role in aging

[149]

OR8B12

Olfactory receptor 8B

Known to be expressed in the brain and is a target of autoimmune response in AD

[83]

OSBPL1A

Like Oxysterol-binding protein-1 (OSBP1)

Modulates processing and trafficking of the amyloid precursor protein

[150]

PCGF2

Polycomb Group Ring Finger 2

May be involved in complexes that participate in amyloid signalling in neurodegenerative disorders

[151]

PDCD5

Programmed Cell Death 5

May play a role in programmed cell death observed in neurodegenerative disorders

[111]

PDE4C

Phosphodiesterase 4C

Inhibition of phosphodiesterase investigated for the treatment of AD

[152]

PDZD9

PDZ Domain proteins

Interact with amyloid precursor protein

[153]

PHACTR4

Phosphatase and actin regulator 4

Regulates Actin Dynamics and Cofilin-Actin Rods in AD

[154]

PRKCD

Protein Kinase C Delta

Is associated with a dysregulated Fc Gamma Receptor-mediated phagocytosis pathway in AD

[104]

PRKN

Parkinson Protein 2, E3 Ubiquitin Protein Ligase formerly PARK2

Deubiquitinating Enzymes Regulate PRKN -mediated Mitophagy neurodegenerative disorders

[120]

RAD52

RAD52 Homolog, DNA Repair Protein

Defects in RAD52 Homolog, DNA Repair Protein (RAD52) may contribute to neurodegeneration in AD

[155]

SGK3

Serum/Glucocorticoid Regulated Kinase Family Member 3

May reflect the role of glucocorticoid receptors in AD

[156]

SLC24A2

Solute Carrier Family 24 (Sodium/Potassium/Calcium Exchanger), Member 2

Genomic evidence has shown associations between mutations in SLC24A4 in AD

[157]

SLC30A1

Solute Carrier Family 30 Member 1 (SLC30A1)

Alterations in Zinc Transporter protein observed in the brain of subjects with AD

[158]

SMPD3

Sphingomyelin Phosphodiesterase 3

Deficiency causes progressive cognitive impairment

[91]

SORBS3

Genomic mutations in Sorbin and SH3 Domain Containing 3

Were associated with Alzheimer’s disease

[112]

SPEG UBE2L3

Striated Muscle Enriched Protein Kinase & Ubiquitin Conjugating Enzyme E2 G1

SPEG and UBE2L3 were differentially methylated genes associated with cognitive impairment

[40, 41]

SYTL4

Synaptotagmin Like 4

Exocytosis or secretion from neurological synapses

[92]

TAGLN2

Transgelin 2

Quantitative protein profiling of Hippocampus showed that Transgelin 2 (TAGLN2) expression increased during human aging [159]

[159]

TBATA

Thymus, Brain And Testes Associated

Role in neurite outgrowth increased in the circulation in AD

[114]

TNF

Tumor Necrosis Factor

TNF degradation products in plasma were observed herein but a recent review concludes there is no increase in circulating TNF- α in Alzheimer’s disease [115]

[115]

TNFRSF14

TNF Receptor Superfamily Member 14

Genetic Deletion of TNF Receptor Superfamily member II, enhanced AD Pathology in an Mouse Model

[116]

TNIK

TRAF2 and NCK Interacting Kinase

Observed in inclusion body-like structures in cognitively impaired and genetic association study indicated that TNIK gene variants had a significant association with Alzheimer-type dementia risk

[118]

TPH1

Tryptophan Hydroxylase 1

Was mis-regulated in the human hippocampus in AD

[160]

TRAF4

TNF Receptor Associated Factor 4

Expression of TNF Receptor Associated Factor similar to TRAF4 was observed in Mouse Models of Down's Syndrome and Alzheimer’s disease

[117]

TRIML2

Polymorphisms in Tripartite Motif Family-Like 2

TRIM14 associated with Alzheimer’s disease Risk

[119]

VTI1B

Vesicle Transport Through Interaction With T-SNAREs 1B

Cell death occurs upon loss of t-SNAREs that may interact with VTI1B

[121, 122]

WDR82

WD repeat-containing protein 82

Neurodegeneration was associated with mutations in the WD repeat domain 45 (WDR45)

[161]

ZC3H12A

Zinc Finger CCCH-Type Containing 12A Endoribonuclease

Genetic variation in imprinted genes such as ZC3H12A is associated with the risk of late-onset Alzheimer’s disease

[162]

ZNF671

Zinc Finger Proteins nucleic acid binding and transcription

Exome Sequencing identified Alzheimer's-Associated Variants in zinc finger domain protein ZNF655

[163, 164]