BIOMARKERS AND ALZHEIMER’S DISEASE

In those who meet the core clinical criteria, biomarker evidence may increase the certainty that Alzheimer’s disease (AD) is the underlying pathology.1

Biomarker confirmation of AD may improve disease management

Your patient’s initial cognitive complaint or observed impairment may be your trigger to screen, diagnose, and intervene. A key part of the process can be biomarker confirmation to support the diagnosis. While biomarker testing is not currently recommended for routine clinical practice, it may be a useful tool when deemed appropriate by the clinician.1-4 Patients with mild cognitive impairment (MCI) can improve, remain stable, or decline cognitively. Identifying biomarkers can help evaluate risk and guide prognosis. The use of biomarker assessment can help your patients to start navigating the journey today.1,5-8

Mild Cognitive Impairment (MCI): The Path to Alzheimer’s Disease (AD) Intervention1-4,9,10

Potential utility for biomarker confirmation

Amyloid beta biomarkers may help2:

  • Support the underlying etiology of the clinical syndrome in an individual with MCI (important for choosing an appropriate intervention or disease management)
  • Determine the likelihood of cognitive and functional progression to a more severe stage of AD within a defined period of time

Biomarkers focused on AD

There are a wide variety of biomarkers available for neuropathological diagnosis of AD. For instance, positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) tests can determine whether amyloid beta (Aβ) pathology is present in the brain and are currently considered valid proxies for neuropathologic changes of AD.11

Many other biomarkers that are commonly used in research are non-specific indicators of neuronal damage. And while magnetic resonance imaging (MRI) is widely available and recommended as part of the diagnostic criteria, especially to rule out other possible causes, it lacks molecular specificity and cannot confirm AD pathology.12

Methods of evaluating amyloid beta

PET Imaging

Amyloid PET imaging uses radiotracers to bind to amyloid plaques in the brain. The PET scanner detects the radiotracers and provides a brain scan that offers high diagnostic accuracy and localized information.12-15

  • Amyloid PET tracers that bind to aggregated Aβ peptides in amyloid plaques provide a means to directly assess relative brain amyloid pathology 
  • The use of in vivo tracers helps establish biomarker relationships with changes in cognition and neurodegeneration, and can help support a diagnosis

Amyloid PET provides an image of Aβ aggregation11,16

Images from Huang CC, et al, used under CC BY 4.0, https://creativecommons.org/licenses/by/4.0/.

CSF Test

Cerebrospinal fluid, obtained via a lumbar puncture, provides assessment of brain pathology and can measure multiple biomarkers.2,3,17,18

  • Levels of amyloid beta in CSF reflect the presence of cerebral amyloid beta deposits  
  • The CSF AB42/40 ratio is a more accurate biomarker of clinical AD, with less variability in assays than CSF AB42 alone
  • There is evidence to suggest that Aβ alterations in CSF occur earlier than they are detectable by Aβ-PET

CSF is collected between the 3rd and 4th, or 4th and 5th vertebrae19,20

Increase your understanding of biomarkers with the Aβ Test Overview

Measures of amyloid beta by CSF and amyloid PET imaging are strongly and inversely correlated, reflecting Aβ deposition in the brain.2

Clinical management is responsive to a biomarker-confirmed diagnosis of AD

As the IDEAS Study has shown, accurate biomarker assessment increases the clinician’s confidence in AD diagnosis and allows for appropriate changes in management, including medication selection and counseling.21

If interventions that target the underlying pathology of AD become available, biomarkers may become more broadly used to identify the stage.22

The Alzheimer’s Care Locator

The Alzheimer’s Care Locator can help you find an Alzheimer’s specialist or diagnostic center for amyloid beta (Aβ) testing.

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References

1.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263-269.
2.
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270-279.
3.
Shaw LM, Arias J, Blennow K, et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers Dement. 2018;14(11):1505-1521.
4.
Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9(1):e1-e16.
5.
Cordell CB, Borson S, Boustani M, et al; and Medicare Detection of Cognitive Impairment Workgroup. Alzheimer’s Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimers Dement. 2013;9(2):141-150.
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Michels TC, Tiu AY, Graver CJ. Neuropsychological evaluation in primary care. Am Fam Physician. 2010;82(5):495-502.
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Alzheimer’s Disease International. World Alzheimer Report 2011: the benefits of early diagnosis and intervention. https://www.alz.co.uk/research/world-report-2011. Accessed February 20, 2020.
8.
Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: mild cognitive impairment: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(3):126-135.
9.
Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551-2561.
10.
Crous-Bou M, Minguillon C, Gramunt N, Molinuevo JL. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimers Res Ther. 2017;9(1):71. doi:10.1186/s13195-017-0297-z.
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Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-562.
12.
Johnson KA, Fox NC, Sperling RA, Klunk WE. Brain imaging in Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(4):a006213. doi:10.1101/cshperspect.a006213.
13.
Suppiah S, Didier M-A, Vinjamuri S. The who, when, why, and how of PET amyloid imaging in management of Alzheimer’s disease—review of literature and interesting images. Diagnostics (Basel). 2019;9(2):65. doi:10.3390/diagnostics9020065.
14.
Lashley T, Schott JM, Weston P, et al. Molecular biomarkers of Alzheimer’s disease: progress and prospects. Dis Model Mech. 2018;11(5):dmm031781. doi:10.1242/dmm.031781.
15.
Wong DF, Rosenberg PB, Zhou Y, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir F 18). J Nucl Med. 2010;51(6):913-920.
16.
Huang CC, Hsiao IT, Huang CY, et al. Tau PET with 18F-THK-5351 Taiwan patients with familial Alzheimer’s disease with the APP p.D678H mutation. Front Neurol. 2019;10:503. doi:10.3389/fneur.2019.00503.
17.
Lewczuk P, Matzen A, Blennow K, et al. Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis. 2017;55(2):813-822.
18.
Palmqvist S, Mattsson N, Hansson O; Alzheimer’s Disease Neuroimaging Initiative. Cerebrospinal fluid analysis detects cerebral amyloid-β accumulation earlier than positron emission tomography. Brain. 2016;139(pt 4):1226-1236.
19.
Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst). 2017;8:111-126.
20.
Khoury R, Ghossoub E. Diagnostic biomarkers of Alzheimer’s disease: a state-of-the-art review. Biomarkers Neuropsychiatry. 2019;1:100005. http://doi.org/10.1016/j.bionps.2019.100005.
21.
Rabinovici GD, Gatsonis C, Apgar C, et al. Association of amyloid positron emission tomography with subsequent change in clinical management among Medicare beneficiaries with mild cognitive impairment or dementia. JAMA. 2019;321(13):1286-1294.
22.
Alzheimer's Association. Alzheimer's Association Report: 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020;16(3):391-460.

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