A premise is a statement that an argument’s claims will induce or justify a conclusion.
Alzheimer’s Disease (AD) research has been guided by psychiatric mental disorders’ methodology for cognitive impairment. Such syndrome methodology used for Alzheimer’s Disease and Related Dementia (ADRD) clinical trials have failed to produce a meaningful intervention during the last two decade. The following premises illustrate the need for a biological focus and PREVENTION acceleration as well as more in-depth biology research of the Tau protein, the Brain’s immune system and AD risk factors.
1. Alzheimer’s Disease begins with Neurodegeneration (neuron loss) in the Transentorhinal Cortex.
2. Neurodegeneration is caused by an unknown Tau Fibrils and Tangles trigger.
3. Tau Fibrils and Tangles are trigger by an unknown amyloid aggregate accumulation level.
4. Once the Tau protein becomes involved, AD decline progresses through Tauopathy and amyloid no longer has a progressive role.
5 The Tau protein involvement creates uncertainty due to the limited knowledge of both the protein isoforms, as well as the brain’s immune system.
6. Amyloid aggregate accumulation occurs for many years before triggering Tau Fibrils and Tangles.
7. Stop Amyloid aggregate accumulation before triggering Tau Fibrils and Tangles and PREVENT Alzheimer’s Disease.
8. Failed trial drugs Aducanumab, Solanezumab, Gantenerumab have demonstrated stopping accumulation along with removal of amyloid.
9. Unapproved Biological Biomarkers for Amyloid and Tau are needed to assure confirmation of AD, as well as managing cognitive impairment.
10. Alzheimer’s Disease begins in the Transentorhinal and Entorhinal Cortex (EC) in the Brain’s Temporal Lobe.
11. Neurodegenerations occurs for many years before AD cognitive impairment symptoms are diagnosed.
12 Symptomatic AD begins with the diagnosis of cognitive impairment.
13. Alzheimer’s Disease becomes Dementia when the patient can no longer self-sustain Activities of Daily Living (ADL).
14. Neurodegeneration due to aging increases research complexity, and AD diagnosis.
15. Once neurodegeneration begins, cure is not possible as re-creation of lost neurons is currently not possible.
Bruce’s Recommended Priorities\
1. Accelerate AD prevention for Asymptomatic candidate.
2. Prioritize research of the Tau Protein and its pathway, along with the Brain’s immune system.
3. Focus Care Investment on Dementia as define in #13.
4 Accelerate approval of Biological Biomarkers.
5. Encourage Lifestyle management and education for Mild Cognitive Impairment (MCI) and Symptomatic AD patients. Play the cards dealt.