[Main Title Screen]
Caption: Hallmark Biomarkers of Alzheimer’s Disease
[Lilly promotional code line and logo at bottom]
Caption: PP-AD-US-0294 3/2022 © Lilly USA, LLC 2022. All rights reserved.
[Begin with outline of person, highlight brain and bring rotating brain to the foreground.]
Narrator: Alzheimer’s disease is a progressive brain disorder that causes a gradual and irreversible loss of higher brain functions, leading to dementia and eventually death due to the debility associated with this disease.1,2
[Window-out key images – Titled visuals of: amyloid plaque, neurofibrillary tangles, and neuronal death.]
Caption: Amyloid Plaque
Caption: Neurofibrillary Tangles
Caption: Neuronal Death
Narrator: Pathologic hallmarks of Alzheimer’s disease include amyloid plaques, neurofibrillary tangles, and degeneration and loss of neurons and their synapses.1,3,4
Narrator: The development of biomarkers has helped to clarify the likely sequence of events that occurs in people with Alzheimer’s disease.5,6
[Animated visuals of different a-beta peptide formations, tau, and NFTs]
Narrator: While there are many unanswered questions, the prevailing theory suggests that abnormal production and clearance of the peptide in the brain called amyloid beta, or A-beta, initiates a complex series of pathological and toxic events.5,6
[Cliff Jack Figure – first visual includes only the a-beta line on graph along with axes labeling]
Clinical disease stage
Narrator: A series of pathological events occur at different stages of the disease, as shown here in this prominent model of Alzheimer’s disease.7
This sequence of events is expressed as a hypothetical model of Alzheimer’s disease that describes a decades-long process beginning with the accumulation of A-beta in the brain,7
[Cliff Jack Figure – includes both a-beta and tau lines]
Narrator: …followed by the development of tau pathology,7
[Cliff Jack Figure – includes the 1) a-beta, 2) tau, 3) brain structure lines on graph]
Narrator: … synaptic dysfunction and neuronal death.7
[Cliff Jack Figure – includes the 1) a-beta, 2) tau, and 3) brain structure,4) memory and 5) clinical function lines on graph
Animated entry of oblong circle appears around Med/Clin Fxn lines
Next – a-beta line is circled]
Narrator: By the time that even subtle signs of dementia are apparent clinically, it is relatively late in the disease process and neuronal destruction has already begun.3,7
Based upon this model, the earliest pathological event is the abnormal accumulation of forms of A-beta.6,7,8
- Mayeux R and Stern Y. Epidemiology of Alzheimer Disease. In: Selkoe DJ, Mandelkow E, and Holtzman DM, ed. The Biology of Alzheimer Disease. New York: Cold Spring Harbor Laboratory Press; 2012:1-19.
- Alzheimer’s Disease Education & Referral (ADEAR) Center. Alzheimer's Disease: Fact Sheet. NIH Publication No. 11-6423 12 July 2021. Available at http://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet. Accessed October 21, 2021.
- Serrano-Pozo A, Frosch MP, Masliah E, and Hyman BT. Neuropathological Alterations in Alzheimer Disease. In: Selkoe DJ, Mandelkow E, and Holtzman DM, ed. The Biology of Alzheimer Disease. New York: Cold Spring Harbor Laboratory Press; 2012:1-23.
- Aisen PS, Cummings J, Jack CR Jr, et al. On the path to 2025: understanding the Alzheimer's disease continuum. Alzheimers Res Ther. 2017;9(1):1-10.
- Blennow K, Zetterberg H, Fagan AM. Fluid Biomarkers in Alzheimer Disease. In: Selkoe DJ, Mandelkow E, and Holtzman DM, ed. The Biology of Alzheimer Disease. New York: Cold Spring Harbor Laboratory Press; 2012:1-23.
- Selkoe DJ and Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med (2016)8:595-608.
- Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. (2010) Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurology. 9(1):119-28.
- Selkoe DJ. (2011) Alzheimer Disease. Cold Spring Harbor Perspectives Biology. 3(7):1-17.