General Information:

Id: 658
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Gotz J et al.(2008) An update on the toxicity of Abeta in Alzheimers disease. Neuropsychiatr Dis Treat 4: 1033-1042 [PMID: 19337449]

Interaction Information:

Comment Alzheimer's disease is characterized histopathologically by deposition of insoluble forms of the peptide Abeta and the protein tau in brain. Abeta (amyloid beta peptide) is the principal component of amyloid plaques and tau of neurofibrillary tangles.
Formal Description
Interaction-ID: 3505

increases_quantity of

Comment Alzheimer's disease is characterized histopathologically by deposition of insoluble forms of the peptide Abeta and the protein tau in brain. Abeta (amyloid beta peptide) is the principal component of amyloid plaques and tau of neurofibrillary tangles.
Formal Description
Interaction-ID: 3507

increases_quantity of

Comment The extracellular plaques and the intracellular neurofibrillary tangles are the key histopathological hallmarks of AD.
Formal Description
Interaction-ID: 3509

is localized in

cellular component

intracellular

Comment The extracellular plaques and the intracellular neurofibrillary tangles are the key histopathological hallmarks of AD.
Formal Description
Interaction-ID: 3510

is localized in

cellular component

extracellular region

Comment The major proteinaceous component of the amyloid plaques is a 40- to 42-amino acid polypeptide termed Abeta (Abeta40 and Abeta42), which is derived by proteolytic cleavage from the amyloid precursor protein, APP, as part of normal cellular metabolism. Abeta42 is the more fibrillogenic and neurotoxic species. Recent evidence suggests that Abeta40 may prevent Abeta42 from aggregating and forming plaques.
Formal Description
Interaction-ID: 3512

increases_quantity of

Comment Neurofibrillary lesions are found in cell bodies and apical dendrites as neurofibrillary tangles, in distal dendrites as neuropilthreads, and in the abnormal neurites that are associated with some beta-amyloid plaques (neuritic plaques).
Formal Description
Interaction-ID: 3514

increases_quantity of

Comment Neurofibrillary lesions are found in cell bodies and apical dendrites as neurofibrillary tangles, in distal dendrites as neuropilthreads, and in the abnormal neurites that are associated with some beta-amyloid plaques (neuritic plaques).
Formal Description
Interaction-ID: 3519

is localized in

cellular component

dendrite

Comment Under pathological conditions, tau is hyperphosphorylated, which means that it is phosphorylated to a higher degree at physiological sites, and at additional “pathological” sites. Phosphorylation tends to dissociate tau from microtubules. Tau also undergoes a conformational change which likely assists in differential phosphorylation.
Formal Description
Interaction-ID: 3520

increases_activity of

protein modification

MAPT-hyperphos

Comment In familial AD, autosomal dominant mutations have been identified in three genes: APP and the presenilin 1 (PS1) and presenilin 2 (PS2) genes.
Formal Description
Interaction-ID: 3521

gene/protein mutant

PSEN1-mut

increases_activity of

Comment In familial AD, autosomal dominant mutations have been identified in three genes: APP and the presenilin 1 (PS1) and presenilin 2 (PS2) genes.
Formal Description
Interaction-ID: 3522

gene/protein mutant

PSEN2-mut

increases_activity of

Comment In familial AD, autosomal dominant mutations have been identified in three genes: APP and the presenilin 1 (PS1) and presenilin 2 (PS2) genes.
Formal Description
Interaction-ID: 3523

gene/protein mutant

APP-mut

increases_activity of

Comment AD is characterized by early memory deficits, followed by a gradual erosion of other cognitive functions such as judgment, verbal fluency and orientation. The most severe neuropathological changes occur in the hippocampal formation, followed by the association cortices and subcortical structures, including the amygdala and the nucleus basalis of Meynert.
Formal Description
Interaction-ID: 3524

decreases_activity of

Comment Aging specifically increased the sensitivity of mitochondria to oligomeric Abeta42 damage indicating that while oligomeric and fibrillar Abeta42 are both toxic, they exert different degrees of toxicity in mitochondria from older animals.
Formal Description
Interaction-ID: 3525

process

aging

increases_activity of

increasing the sensitivity of mitochondria to oligomeric Abeta42 damage
Comment Aging specifically increased the sensitivity of mitochondria to oligomeric Abeta42 damage indicating that while oligomeric and fibrillar Abeta42 are both toxic, they exert different degrees of toxicity in mitochondria from older animals.
Formal Description
Interaction-ID: 3527

process

aging

decreases_activity of

cellular component

mitochondrion

Comment Aging specifically increased the sensitivity of mitochondria to oligomeric Abeta42 damage indicating that while oligomeric and fibrillar Abeta42 are both toxic, they exert different degrees of toxicity in mitochondria from older animals.
Formal Description
Interaction-ID: 3528

decreases_activity of

cellular component

mitochondrion

Comment Fyn is an interaction partner of tau.
Formal Description
Interaction-ID: 3532

gene/protein

FYN

interacts (colocalizes) with

gene/protein

MAPT

Drugbank entries Show/Hide entries for FYN
Comment Abeta can disrupt mitochondrial cytochrome c oxidase activity.
Formal Description
Interaction-ID: 3550

gene/protein

Amyloid beta peptide

decreases_activity of

complex/PPI

Mitochondrial respiratory chain complex IV

Comment AD is characterized by early memory deficits, followed by a gradual erosion of other cognitive functions such as judgment, verbal fluency and orientation. The most severe neuropathological changes occur in the hippocampal formation, followed by the association cortices and subcortical structures, including the amygdala and the nucleus basalis of Meynert.
Formal Description
Interaction-ID: 19174

increases_activity of

phenotype

cognitive impairment

Comment Abeta42 is the more fibrillogenic and neurotoxic species. Recent evidence suggests that Abeta40 may prevent Abeta42 from aggregating and forming plaques.
Formal Description
Interaction-ID: 80152

increases_quantity of

complex/PPI

Amyloid beta peptide (fibrillar)