From NCBI Gene: Alzheimer's diseaseFrom UniProt: Alzheimer disease (AD): Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. [MIM:104300]

     From NCBI Gene: This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016] From UniProt: Likely to be a multifunctional endocytic receptor, that may be implicated in the uptake of lipoproteins and of proteases. Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. Binds the receptor-associated protein (RAP). Could play a role in cell-cell interaction. Involved in APP trafficking to and from the Golgi apparatus. It probably acts as a sorting receptor that protects APP from trafficking to late endosome and from processing into amyloid beta, thereby reducing the burden of amyloidogenic peptide formation. Involved in the regulation of smooth muscle cells migration, probably through PLAUR binding and decreased internalization.

The following transcription factors affect gene expression:

• RORalpha2
• E2F-1
• GATA-1
• C/EBPbeta

Tissue specificity:

Expressed mainly in brain, where it is most abundant in the cerebellum, cerebral cortex and the occipital pole; low expression in the putamen and the thalamus. Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease. According to PubMed:9157966, found in spinal cord, testis, liver, kidney and pancreas with detectable levels in placenta, lung and heart. According to PubMed:8940146, expressed in the prostate, ovary, thyroid and spleen, but not found in kidney, liver, lung, skeletal muscle, bone marrow and adrenals.

Molecular Function:

• Beta-Amyloid Binding
• Transmembrane Signaling Receptor Activity
• Low-Density Lipoprotein Particle Binding
• Adp-Ribosylation Factor Binding

Biological Processes:

• Protein Targeting To Golgi
• Protein Targeting
• Protein Targeting To Lysosome
• Lipid Transport
• Post-Golgi Vesicle-Mediated Transport
• Receptor-Mediated Endocytosis
• Cholesterol Metabolic Process
• Regulation Of Smooth Muscle Cell Migration
• Negative Regulation Of Protein Oligomerization
• Negative Regulation Of Map Kinase Activity
• Protein Retention In Golgi Apparatus
• Positive Regulation Of Protein Catabolic Process
• Negative Regulation Of Neurogenesis
• Protein Maturation
• Positive Regulation Of Protein Exit From Endoplasmic Reticulum
• Negative Regulation Of Neuron Death
• Negative Regulation Of Beta-Amyloid Formation
• Positive Regulation Of Choline O-Acetyltransferase Activity
• Negative Regulation Of Tau-Protein Kinase Activity
• Positive Regulation Of Er To Golgi Vesicle-Mediated Transport
• Positive Regulation Of Early Endosome To Recycling Endosome Transport
• Negative Regulation Of Aspartic-Type Endopeptidase Activity Involved In Amyloid Precursor Protein Catabolic Process
• Negative Regulation Of Metalloendopeptidase Activity Involved In Amyloid Precursor Protein Catabolic Process
• Positive Regulation Of Protein Localization To Early Endosome
• Negative Regulation Of Neurofibrillary Tangle Assembly
• Positive Regulation Of Endocytic Recycling