Therapeutic considerations for APOE and TOMM40 in Alzheimers disease: A tribute to Allen Roses MD

Document Type

Article

Abstract

Introduction: Four years ago this Autumn, pioneering neurologist Prof. Allen. D. Roses passed away. Hence, we have taken time to reflect on his work and legacy in Alzheimer’s disease (AD) research. Prof. Roses rejected the widely accepted amyloid hypothesis, which identifies amyloid beta (Aβ) protein accumulation within the brain as the cause of AD. Instead, he proposed that the epsilon type 4 allele of apolipoprotein (APOE- Ɛ4) and translocase of outer mitochondrial membrane 40 homolog (TOMM40) were preeminent factors in the pathogenesis and progression of AD, particularly in late-onset AD (LOAD). This rejection of the amyloid hypothesis has generated new investigations into APOE and TOMM40 as risk factors for AD. Areas covered: We discuss the contributions of Prof. Roses to AD research, describe how APOE-Ɛ4 and TOMM40 have been posited to trigger neuropathological changes leading to AD, and explore paths to future clinical applications built on the foundations of his research. Expert opinion: The unconventional methodology of targeting APOE and TOMM40 offers great potential for the development of effective preventive and disease-modifying AD interventions. Future preclinical and clinical investigations will greatly benefit from the groundbreaking scientific discoveries of Prof. Roses.

Publication Date

1-1-2021

Publication Title

Expert Opinion on Investigational Drugs

ISSN

13543784

E-ISSN

17447658

Volume

30

Issue

1

First Page

39

Last Page

44

PubMed ID

33455481

Digital Object Identifier (DOI)

10.1080/13543784.2021.1849138

Link to Full Text

Share

COinS