AMYLOID BETA CASCADE HYPOTHESIS

Alzheimer’s disease (AD) is thought to be caused by a sequence of events triggered by the accumulation of amyloid beta.1

How the amyloid beta cascade leads to neurological damage

In people with AD, the presence of amyloid beta is believed to trigger a pathological cascade that may promote the abnormal phosphorylation of tau protein, which leads to the formation of neurofibrillary tangles within neurons.1,2

Together, abnormal accumulation of amyloid beta plaques and neurofibrillary tangles can impair neuronal function and may cause neurodegeneration (atrophy).1,3

These pathological changes of Alzheimer’s disease are thought to begin decades before any clinical symptoms appear.²

Pathological Changes Across Alzheimer's Disease Stages4

To learn more about a specific disease stage, use the tappableclickable symbols.

FPO Progression Chart Grid
FPO Progression Chart - Amyloid Beta Accumulation Line
FPO Progression Chart - Synaptic Dysfunction Line
FPO Progression Chart - Tau-Mediated Neuronal Injury Line
FPO Progression Chart - Brain Structure Line
FPO Progression Chart - cognition Line
FPO Progression Chart - Line
FPO Progression Chart - ab icon active FPO Progression Chart - ab icon FPO Progression Chart - Synaptic Dysfunction icon FPO Progression Chart - Synaptic Dysfunction active icon FPO Progression Chart - Tau icon FPO Progression Chart - t active icon FPO Progression Chart - Brain Structure icon FPO Progression Chart - Brain Structure active icon FPO Progression Chart - Cognition icon FPO Progression Chart - Cognition active icon FPO Progression Chart - Clinical Function icon FPO Progression Chart - Clinical Function active icon

A (Amyloid Beta Accumulation)

It is believed that amyloid beta accumulation starts decades before the onset of clinical symptoms, setting off a cascade that leads to the formation of neurofibrillary tangles and the initiation of neurodegeneration in Alzheimer’s disease.4

Synaptic Dysfunction

When amyloid beta is no longer cleared from the brain properly, it accumulates and is widely believed to lead to synaptic dysfunction and neurodegeneration long before the first symptoms of Alzheimer’s disease start to become visible.4

Tau-mediated Neuronal Injury

The accumulation of amyloid beta is believed to promote the abnormal phosphorylation of tau protein, which leads to the formation of neurofibrillary tangles within neurons.4

Brain Structure

Together, abnormal accumulation of amyloid beta plaques and neurofibrillary tangles may cause neurodegeneration through neuronal and synaptic loss (atrophy).4

Cognition

MCI due to AD may show evidence of disease pathology along with impairment in 1 or more cognitive domains that does not interfere with daily functioning.7

Clinical Function

Initially, amyloid beta plaques accumulate in the centers of higher mental function and those related to learning and memory. Ultimately, plaques compromise areas that regulate attention, emotion, and various other activities, severely impacting daily life.8,9

*Mild cognitive impairment.

Adapted from Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9(1):119-128, with permission from Elsevier. https://www.sciencedirect.com/journal/the-lancet-neurology.

A signal for intervention

According to the cascade hypothesis, amyloid beta accumulation is the earliest marker of Alzheimer's disease pathology, occurring upstream of synaptic dysfunction and tau-mediated neuronal injury.5

This makes biomarker confirmation via amyloid positron emission tomography (PET) scan or cerebrospinal fluid (CSF) test all the more important. The diagnostic value of AD as the cause of MCI provides the clinician an opportunity to intervene before greater neuronal damage occurs and more cognition and function are lost.6

See how testing for amyloid beta can complete the diagnosis

Support an MCI due to AD diagnosis with biomarkers.

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