The intersection of amyloid beta and tau at synapses in Alzheimer’s disease

By T. Spires-Jones, Bradley T. Hyman. Neuron, 2014

1,070 citations recorded by the source corpus.

Summary The collapse of neural networks important for memory and cognition, including death of neurons and degeneration of synapses, causes the debilitating dementia associated with Alzheimer’s disease (AD). We suggest that synaptic changes are central to the disease process. Amyloid beta and tau form fibrillar lesions that are the classical hallmarks of AD. Recent data indicate that both molecules may have normal roles at the synapse, and that the accumulation of soluble toxic forms of the proteins at the synapse may be on the critical path to neurodegeneration. Further, the march of neurofibrillary tangles through brain circuits appears to take advantage of recently described mechanisms of trans-synaptic spread of pathological forms of tau. These two key phenomena, synapse loss and the spread of pathology through the brain via synapses, make it critical to understand the physiological and pathological roles of amyloid beta and tau at the synapse.

Subfields: Cellular and Molecular Neuroscience, Pharmacology, Physiology

View Paper: https://www.semanticscholar.org/paper/1f75443a504e103fec800482bcc57ce8962a5811

How researchers see this paper

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

In Pharmacology

1. Suzanne L. Baker
2. William J. Jagust
3. Gil D. Rabinovici
4. Samuel N. Lockhart

In Physiology

1. Bruce L. Miller
2. Suzanne L. Baker
3. William J. Jagust
4. Gil D. Rabinovici
5. Samuel N. Lockhart

Citations in the corpus

• A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics (2022, background): “Plaque formation disrupts hippocampal circuitry leading to poor short-term memory consolidation into long-term traces [34].”
• PET Imaging of Tau Deposition in the Aging Human Brain (2016, neutral): “Both tau and Ab cause synaptic damage in soluble and fibrillar forms, individually and together (Spires-Jones and Hyman, 2014); where and how they interact and whether they enable each other’s spread is still widely unknown, although APOE allele status and GSK3 activity have, among others, been iden”
• Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. (2016, background): “Tau pathology has a devastating effect on synaptic function (Gomez-Isla et al., 1997; Beharry et al., 2014; Spires-Jones and Hyman, 2014) and relates more strongly to cognitive functions during life than does amyloid-b (Arriagada et al., 1992; Nelson et al., 2012; van Rossum et al., 2012; Rolstad…”