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Biomarker innovation in Alzheimer’s disease Learning Zone
Biomarker innovation in Alzheimer’s disease Learning Zone

Alzheimer’s disease overview

Read time: 100 mins
Last updated:19th Oct 2022
Published:19th Oct 2022

Unmet needs in Alzheimer’s disease management

Listen to Charlotte Teunissen, Professor of Neurochemistry at the Vrije Universiteit Amsterdam, Netherlands, discuss unmet needs in Alzheimer's disease (AD). In the second video clip, Professor Teunissen summarises AD, and why curative treatments are urgently needed.

An overview of Alzheimer’s disease, and why curative treatments are needed
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An overview of Alzheimer’s disease, and why curative treatments are needed
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Alzheimer's disease pathophysiology

Alzheimer’s disease (AD) is the most common cause of dementia, representing 60–80% of cases1. AD prevalence in 2018 was estimated at 50 million people worldwide, which is projected to double in Europe, and triple worldwide by 20502,3.

AD is characterised by brain tissue abnormalities, which are diagnostic biomarkers of the disease and targets for medication development3. The abnormalities in AD include accumulation of3:

  • Amyloid-β (Aβ) plaques (Figure 1)
  • Aβ oligomers outside of neurons
  • Twisted fibrils of tau proteins inside neurons (Figure 2)

BioAlz_T1_Fig2.png

Figure 1. An example of amyloid-β pathology in Alzheimer’s disease (Adapted4). Amyloid-β fibrils accumulate in the neocortex; this accumulation targets medial parietal and frontal areas (red). Then, other cortical areas are affected (orange), with primary motor and sensory areas affected last (yellow). Finally, the brainstem and cerebellum are damaged (blue). Arrows indicate order of damaged brain regions; left-side images show interior midsagittal section; right-side images show exterior sagittal view. The sequence of neuropathology is left to right, top to bottom.

BioAlz_T1_Fig3.png

Figure 2. An example of tau neuropathology in Alzheimer’s disease (Adapted4). Tau-tangles emerge in the (trans) entorhinal cortex (dark red), then in the hippocampus and amygdala (red). Other cortical regions of the temporal lobe are next damaged (orange), followed by the medial and lateral parietal cortex and lateral occipital cortex (yellow). Finally, frontal areas (blue), primary motor and sensory areas (dark blue) are affected. Arrows indicate order of damaged brain regions; left-side images show interior midsagittal section; right-side images show exterior sagittal view. The sequence of neuropathology is left to right, top to bottom.

AD is a heterogeneous and complex disease that is challenging for healthcare professionals to differentiate from other forms of dementia3. The National Institute on Aging and Alzheimer’s Association developed the Alzheimer’s Diagnostic Framework to classify AD and differentiate it from non-AD causes of cognitive impairment, following biomarker criteria5. The biomarkers of AD pathology—extracellular deposition of Aβ (‘A’), intracellular tau tangles (‘T’) and neurodegeneration (‘N’)—were included in the ‘A/T/N’ framework5.

Please continue to watch additional expert interviews, download a helpful infographic, and learn more about the current state of biomarkers in Alzheimer’s disease for diagnosis, monitoring disease progression, and more

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Assessing and diagnosing Alzheimer’s disease

Professor Charlotte Teunissen, based at Amsterdam Neuroscience at the Vrije Universiteit Amsterdam, Netherlands, presents two videos: in the first, she outlines available biomarkers for diagnosing Alzheimer's disease (AD), in the second, biomarkers for monitoring AD progression.

What biomarkers are available for diagnosing Alzheimer’s disease?
What biomarkers can effectively monitor Alzheimer's disease progression?
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Diagnosis of Alzheimer’s disease requires specifying a clinical phenotype of Alzheimer’s, and biomarker evidence of neuropathology12

Diagnostic pathway for Alzheimer’s disease

Diagnosis of AD is complex, and involves the use of many clinical tools and practices, across several stages (Figure 5)3,12,64.

BioAlz_T1_Fig9.png

Figure 5. Alzheimer’s disease diagnostic pathway, and potential roles of health care professionals within the care team (Adapted64). AD, Alzheimer’s disease; cog, cognitive; HCP, health care professional.

The initial detection stage occurs when healthcare professionals (HCP) are made aware of cognitive concerns or have clinical evidence of cognitive impairment. Subsequent diagnostic stages—assessing for cognitive impairment and/or a high probability of AD pathology, and differentiating AD from other causes of cognitive impairment—involves specialised expertise (Figure 5).

Introduction of an AD specialist to diagnose early-stage AD is recommended59. Following diagnosis of AD through biomarker investigation and determination of treatments by a specialist, treatment and monitoring of patients may be assigned to a patient-centred, multidisciplinary team, with clinical skills across several disciplines (Figure 5).

Please continue to watch additional expert interviews, download a helpful infographic, and learn more about the current state of biomarkers in Alzheimer’s disease

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Treating Alzheimer’s disease

Charlotte Teunissen, Professor of Neurochemistry at Vrije Universiteit Amsterdam, Netherlands, discusses risk factors for Alzheimer's disease (AD) that can be modified with lifestyle (non-pharmacological) interventions. In the second video, Professor Teunissen summarises the pharmacological drugs that are being developed for treating AD pathology.

What treatments are being developed to target Alzheimer's disease pathology?
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Please continue to watch additional expert interviews, download a helpful infographic, and learn more about the current state of biomarkers in Alzheimer’s disease

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Biomarkers in Alzheimer’s Disease

Charlotte Teunissen, Professor of Neurochemistry at Amsterdam Neuroscience at the Vrije Universiteit Amsterdam, Netherlands, speculates about biomarkers for Alzheimer's disease (AD) becoming more widely used in the clinic.

 

Please continue to download the fluid biomarkers infographic, and to learn more about the current state of biomarkers in Alzheimer’s disease

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Biomarker innovations in Alzheimer’s disease

Charlotte Teunissen, Professor of Neurochemistry at the Vrije Universiteit Amsterdam, describes the five-step process for developing Alzheimer's disease (AD) biomarkers. In the second video, she explains why this process has accelerated in recent years.

What is the development process for Alzheimer’s disease biomarkers?
Is biomarker development for Alzheimer's disease accelerating?
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Development of blood-based biomarkers for AD could improve the diagnostic workup of Alzheimer’s disease3,4,29,30,118

Unmet needs in biomarkers for Alzheimer’s disease

Positron emission tomography (PET) and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers are not widely available and are costly (PET) or viewed as invasive (CSF). These factors could restrict their use in routine clinical practice to a more limited number of specialised centres3,4,29,30,118.

Thus, there is a pressing unmet medical need to identify cost-effective biomarkers for AD that are viewed as less invasive to patients, and widely available. Blood-based biomarkers could fulfil this need (Figure 9)29,30.

BioAlz_T1_Fig8.png

Figure 9. Potential use of diagnostic blood-based biomarkers for Alzheimer’s disease in primary care settings (Adapted4). Note: some patients with high probability of ND could be referred directly to specialist care; some patients with low probability ND could be followed up in primary care. CSF, cerebrospinal fluid; PET, positron-emission tomography.

Please continue to watch additional expert interviews, download a helpful infographic, and learn more about the current state of biomarkers in Alzheimer’s disease

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References

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