Alzheimer's disease

progressive, neurodegenerative disease characterized by memory loss

German psychiatrist and neuropathologist (1864–1915)

free radical toxicity

group of peptides, several of which can form oligomeric cation-selective peptide channels

Milnacipran (trade names Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia, major depressive disorder, and neuropathic pain. In the US, it is solely approved for the treatment of fibromyalgia, even though it is also approved for the treatment of major depressive disorder (but not fibromyalgia) in other countries (e.g. France).

mammalian protein found in Homo sapiens

mammalian proteins found in Homo sapiens

brain function syndrome

Neprilysin (; also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10) and common acute lymphoblastic leukemia antigen (CALLA)) is an enzyme that in humans is encoded by the MME gene. Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. It also degrades the amyloid beta peptide whose abnormal folding and aggregation in neural tissue has been implicated

thumbnail|right|The Necroptosis Signaling Pathway Necroptosis is a programmed form of necrosis and one of the many modalities of programmed cell death that has been described insofar. Conventionally, necrosis is associated damage caused by traumatic external forces, such as mechanical damage, heat, osmotic pressure and disruption by certain parasites. In contrast to orderly, programmed cell death via apoptosis, necrosis in this sense doesn't involve biological processes happening within the cell. The content of the cell only matters after its death: released into the extracellular environment,

mammalian protein found in Homo sapiens

Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors.

Levomilnacipran, sold under the brand name Fetzima, is an antidepressant, used for the treatment of major depressive disorder in adults. It is the levorotatory enantiomer of milnacipran, and has similar effects and pharmacology, acting as a serotonin–norepinephrine reuptake inhibitor.

intracellular mass of paired, helically wound protein filaments lying in the cytoplasm of neuronal cell bodies and neuritic cell processes

Bradyphrenia is the slowness of thought common to many disorders of the brain. Disorders characterized by bradyphrenia include Parkinson's disease and forms of schizophrenia consequently causing a delayed response and fatigue. Patients with bradyphrenia may describe or may manifest slowed thought processes, evidenced by increased latency of response and also involve severe memory impairment and poor motor control. The word 'bradyphrenia' originates from the ancient Greek meaning 'slow mind.'

progressive language and speech disorder

group of neurons in the brain

CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

chemical compound

Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes, called PSEN1 (located on chromosome 14 in humans) that codes for presenilin 1 (PS-1) and PSEN2 (on chromosome 1 in humans) that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human p

Sundowning, or sundown syndrome, prevalent among people with some form of dementia, is characterized by increased confusion and restlessness beginning in the late afternoon and early evening. The term sundowning was coined by nurse Lois K. Evans in 1987 due to the association between the person's increased confusion and the setting of the sun.

first person diagnosed with Alzheimer's disease (1850-1906)

chemical compound

Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.

Presenilin-2 is a protein that (in humans) is encoded by the PSEN2 gene.

aggregation of mis-folded proteins

Triggering receptor expressed on myeloid cells 2 (TREM2) is a protein that in humans is encoded by the TREM2 gene. TREM2 is expressed on macrophages, immature monocyte-derived dendritic cells, osteoclasts, and microglia, which are immune cells in the central nervous system. In the liver, TREM2 is expressed by several cell types, including macrophages, that respond to injury. In the intestine, TREM2 is expressed by myeloid-derived dendritic cells and macrophage. TREM2 is overexpressed in many tumor types and has anti-inflammatory activities. It might therefore be a good therapeutic target.

protein complex that has aspartic-type endopeptidase activity, and contains a catalytic subunit, presenilin (PS), that is a prototypical member of the GxGD-type aspartyl peptidases. The complex also contains additional subunits, including nicastrin

chemical compound

Semagacestat (LY-450139) was a candidate drug for a causal therapy against Alzheimer's disease. It was originally developed by Eli Lilly and Elan, and clinical trials were conducted by Eli Lilly. Phase III trials included over 3000 patients, but in August 2010, a disappointing interim analysis, in which semagacestat performed worse than the placebo, led to the trials being stopped.

chemical compound

therapy developed by Naomi Feil for older people with cognitive impairments and dementia

Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the NCSTN gene.

Axona was previously marketed as a medical food for the clinical dietary management of the impairment of metabolic processes associated with mild to moderate Alzheimer's disease. It is a proprietary formulation of fractionated palm kernel oil (caprylic triglyceride), a medium-chain triglyceride. Cericin, the company that makes Axona, states that during digestion, caprylic triglyceride is broken down into ketones, which provide an alternative energy source for the brain. Its use is based on the idea that the brain's ability to use its normal energy source, glucose, is impaired in Alzheimer's di

inclusion bodies for misfolded proteins

', operated by nursing home ', is a gated model village in Weesp, Netherlands. It has been designed specifically as a pioneering care facility for elderly people with dementia. The benefit of using all-day reminiscence therapy at Hogewey, compared to traditional nursing homes, is that the residents with dementia are more active and require less medication.

PSENEN, formally PEN-2 (presenilin enhancer 2), is a protein that is a regulatory component of the gamma secretase complex, a protease complex responsible for proteolysis of transmembrane proteins such as the Notch protein and amyloid precursor protein (APP). The gamma secretase complex consists of PEN-2, APH-1, nicastrin, and the catalytic subunit presenilin. PEN-2 is a 101-amino acid integral membrane protein likely with a topology such that both the N-terminus and the C-terminus face first the lumen of the endoplasmic reticulum and later the extracellular environment. Biochemical studies ha

thumb|Schematic diagram of the multiple domains of SORLA, the protein product of the SORL1 gene. The relative orientations of the domains are drawn to match the ectodomain model of Jensen et al., PNAS (2023), which is also shown on the next figure. From Holstege et al., medRxiv (2023). thumb|Schematic and structure model of the ectodomain of SORLA/SORL1, plus its two dimer interfaces in the middle panel, followed by the way the two interfaces can combine to form a polymeric network and how that network can underlie and stabilize the network of retromer arches on the other side of the tubular m

common behavior in people with dementia

thumb|The humanin gene is found within the 16S rRNA gene (MT-RNR2) in the mitochondrial genome Humanin is a micropeptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry.

GRB2-associated-binding protein 2 also known as GAB2 is a protein that in humans is encoded by the GAB2 gene.

Alzheimer's disease developing before the age of 65