Alzheimer’s disease overview

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 2050^2,3.

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)

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.

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

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.

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

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

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

Development of blood-based biomarkers for AD could improve the diagnostic workup of Alzheimer’s disease^{3,4,29,30,118}

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 centres^{3,4,29,30,118}.

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.

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