Amyloid-β and Tau

By G. Bloom. JAMA Neurology, 2014

1,972 citations recorded by the source corpus.

The defining features of Alzheimer disease (AD) include conspicuous changes in both brain histology and behavior. The AD brain is characterized microscopically by the combined presence of 2 classes of abnormal structures, extracellular amyloid plaques and intraneuronal neurofibrillary tangles, both of which comprise highly insoluble, densely packed filaments. The soluble building blocks of these structures are amyloid-β (Aβ) peptides for plaques and tau for tangles. Amyloid-β peptides are proteolytic fragments of the transmembrane amyloid precursor protein, whereas tau is a brain-specific, axon-enriched microtubule-associated protein. The behavioral symptoms of AD correlate with the accumulation of plaques and tangles, and they are a direct consequence of the damage and destruction of synapses that mediate memory and cognition. Synapse loss can be caused by the failure of live neurons to maintain functional axons and dendrites or by neuron death. During the past dozen years, a steadily accumulating body of evidence has indicated that soluble forms of Aβ and tau work together, independently of their accumulation into plaques and tangles, to drive healthy neurons into the diseased state and that hallmark toxic properties of Aβ require tau. For instance, acute neuron death, delayed neuron death following ectopic cell cycle reentry, and synaptic dysfunction are triggered by soluble, extracellular Aβ species and depend on soluble, cytoplasmic tau. Therefore, Aβ is upstream of tau in AD pathogenesis and triggers the conversion of tau from a normal to a toxic state, but there is also evidence that toxic tau enhances Aβ toxicity via a feedback loop. Because soluble toxic aggregates of both Aβ and tau can self-propagate and spread throughout the brain by prionlike mechanisms, successful therapeutic intervention for AD would benefit from detecting these species before plaques, tangles, and cognitive impairment become evident and from interfering with the destructive biochemical pathways that they initiate.

Subfields: Molecular Biology, Pharmacology, Physiology

View Paper: https://www.semanticscholar.org/paper/12b26084d83b36745bc10fcd6381fe2371c7dd16

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Pharmacology

R. Swerdlow

In Physiology

Citations in the corpus

Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease (2017, background): “In response to this, some now speculate A itself is insufficient to cause the disease, but instead initiates AD by triggering a critical change in tau biology [114, 119, 120].”
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “In the case of AD, these deposits contain β-amyloid proteins and hyperphosphorylated tau protein (tau-P), which, respectively, form extracellular plaques and intracellular fibrillar tangles (125).”
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “neurotoxicity occurs in a tau-dependent manner [299].”
Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “In hippocampal neurons, Aβ also induced the activation of calpain-1 and generated a 17-kDa tau fragment, resulting in neurite degeneration and neuronal death.(137) Meanwhile, the toxic state of tau proteins also influence Aβ production.”