Alzheimer disease; Dementia due to Alzheimer disease
Description
Alzheimer disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2), and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. It was proposed that Abeta forms Ca2+ permeable pores and binds to and modulates multiple synaptic proteins, including NMDAR, mGluR5, and VGCC, leading to the overfilling of neurons with calcium ions. Consequently, cellular Ca2+ disruptions will lead to neuronal apoptosis, autophagy deficits, mitochondrial abnormality, defective neurotransmission, impaired synaptic plasticity, and neurodegeneration in AD. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.
Category
Neurodegenerative disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Disorders with neurocognitive impairment as a major feature
8A20 Alzheimer disease
H00056 Alzheimer disease
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06534 Unfolded protein response
H00056 Alzheimer disease
nt06535 Efferocytosis
H00056 Alzheimer disease
nt06546 IgSF CAM signaling
H00056 Alzheimer disease
Cuyvers E, De Roeck A, Van den Bossche T, Van Cauwenberghe C, Bettens K, Vermeulen S, Mattheijssens M, Peeters K, Engelborghs S, Vandenbulcke M, Vandenberghe R, De Deyn PP, Van Broeckhoven C, Sleegers K
Title
Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study.
Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K
Title
Variant of TREM2 associated with the risk of Alzheimer's disease.
Cerebral amyloid angiopathy; Hereditary cerebral hemorrhage with amyloidosis
Description
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of congophilic material in the vessels of the cortex and leptomeninges. Although CAA most commonly appears in a sporadic form associated with aging, several familial forms of CAA reported to date. Hereditary cystatin C amyloid angiopathy (HCCAA) is a rare, fatal amyloid disease in young people in Iceland caused by a mutation in cystatin C, which is an inhibitor of several cysteine proteinases. It has also been reported that mutations in APP are linked to CAA.
Category
Neurodegenerative disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Metabolic disorders
Other metabolic disorders
5D00 Amyloidosis
H01185 Cerebral amyloid angiopathy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06546 IgSF CAM signaling
H01185 Cerebral amyloid angiopathy
Bugiani O, Giaccone G, Rossi G, Mangieri M, Capobianco R, Morbin M, Mazzoleni G, Cupidi C, Marcon G, Giovagnoli A, Bizzi A, Di Fede G, Puoti G, Carella F, Salmaggi A, Romorini A, Patruno GM, Magoni M, Padovani A, Tagliavini F
Title
Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP.
