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
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.
Reticulate acropigmentation of Kitamura (RAK) is a rare autosomal dominant disorder of cutaneous pigmentation. The typical clinical features are reticulate and sharply demarcated brown macules, affecting the dorsa of the hands and feet. Recently, mutations in ADAM10, encoding a zinc metalloprotease, were identified in patients with RAK.
Category
Skin disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
14 Diseases of the skin
Genetic and developmental disorders affecting the skin
EC23 Genetic disorders of skin pigmentation
H02665 Reticulate acropigmentation of Kitamura
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06535 Efferocytosis
H02665 Reticulate acropigmentation of Kitamura
Kono M, Sugiura K, Suganuma M, Hayashi M, Takama H, Suzuki T, Matsunaga K, Tomita Y, Akiyama M
Title
Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease.
