What have we learned from past failures of investigational drugs for Alzheimer’s disease?

Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease

(2021) Reisa Sperling et al.   JAMA Neurology

Alzheimer's disease

(2021) Philip Scheltens et al.   LANCET

Donanemab in Early Alzheimer’s Disease

(2021) Mark A. Mintun et al.   NEW ENGLAND JOURNAL OF MEDICINE

Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis

(2021) Sarah F Ackley et al.   BMJ-British Medical Journal

Whole‐genome sequencing reveals new Alzheimer's disease–associated rare variants in loci related to synaptic function and neuronal development

(2021) Dmitry Prokopenko et al.   Alzheimers & Dementia

Failure of genetic therapies for Huntington’s devastates community

(2021) Diana Kwon   NATURE

Association of APOE Genotype With Heterogeneity of Cognitive Decline Rate in Alzheimer Disease

(2021) Jing Qian et al.   NEUROLOGY

A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody

(2021) Chad J. Swanson et al.   Alzheimers Research & Therapy

Comparing amyloid-β plaque burden with antemortem PiB PET in autosomal dominant and late-onset Alzheimer disease

(2021) Charles D. Chen et al.   ACTA NEUROPATHOLOGICA

A critical appraisal of tau‐targeting therapies for primary and secondary tauopathies

(2021) Bruno P. Imbimbo et al.   Alzheimers & Dementia

Intranasal Paclitaxel Alters Alzheimer’s Disease Phenotypic Features in 3xTg-AD Mice

(2021) Donna J. Cross et al.   JOURNAL OF ALZHEIMERS DISEASE

The informed road map to prevention of Alzheimer Disease: A call to arms

(2021) Eric McDade et al.   Molecular Neurodegeneration

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease

(2021) Stephen Salloway et al.   NATURE MEDICINE

Can we learn lessons from the FDA’s approval of aducanumab?

(2021) Kathy Y. Liu et al.   Nature Reviews Neurology

The approval of Aduhelm risks eroding public trust in Alzheimer research and the FDA

(2021) Jason Karlawish et al.   Nature Reviews Neurology

Clinical Efficacy, Drug Safety, and Surrogate Endpoints

(2021) Linda A. Hershey et al.   NEUROLOGY

Revisiting FDA Approval of Aducanumab

(2021) G. Caleb Alexander et al.   NEW ENGLAND JOURNAL OF MEDICINE

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

(2021) Julie Gonneaud et al.   Nature Communications

Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer’s disease and frontotemporal dementia

(2021) Sagar Gaikwad et al.   Cell Reports

US Food and Drug Administration Approval of Aducanumab—Is Amyloid Load a Valid Surrogate End Point for Alzheimer Disease Clinical Trials?

(2021) Vincent Planche et al.   JAMA Neurology

Evaluating Effects of Glatiramer Acetate Treatment on Amyloid Deposition and Tau Phosphorylation in the 3xTg Mouse Model of Alzheimer’s Disease

(2021) Dawling A. Dionisio-Santos et al.   Frontiers in Neuroscience

The β-secretase BACE1 in Alzheimer’s disease

(2020) Harald Hampel et al.   BIOLOGICAL PSYCHIATRY

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal‐Dominant Alzheimer's Disease Colombia Trial

(2020) Silvia Rios‐Romenets et al.   Alzheimers & Dementia

Medial temporal lobe connectivity and its associations with cognition in early Alzheimer’s disease

(2020) David Berron et al.   BRAIN

A Perspective on Multi-target Drugs for Alzheimer’s Disease

(2020) Ondrej Benek et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Association of Factors With Elevated Amyloid Burden in Clinically Normal Older Individuals

(2020) Reisa A. Sperling et al.   JAMA Neurology

A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease

(2020) Harald Hampel et al.   Frontiers in Immunology

The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

(2020) Sarah A. Kent et al.   ACTA NEUROPATHOLOGICA

Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia

(2020) Suzanne Craft et al.   JAMA Neurology

Amyloid, tau and risk of Alzheimer’s disease: a Mendelian randomization study

(2020) Chris Ho Ching Yeung et al.   EUROPEAN JOURNAL OF EPIDEMIOLOGY

BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer’s disease brain

(2020) Cyrille Sur et al.   BRAIN

APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches

(2020) Alberto Serrano-Pozo et al.   LANCET NEUROLOGY

Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

(2020) Fangda Leng et al.   Nature Reviews Neurology

A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease

(2019) Francesco Panza et al.   Nature Reviews Neurology

Design and sample size considerations for Alzheimer’s disease prevention trials using multistate models

(2019) Ron Brookmeyer et al.   Clinical Trials

Targeting Huntingtin Expression in Patients with Huntington’s Disease

(2019) Sarah J. Tabrizi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer’s disease

(2019) Michael F. Egan et al.   Alzheimers Research & Therapy

Do anti-amyloid-β drugs affect neuropsychiatric status in Alzheimer’s disease patients?

(2019) Francesco Panza et al.   AGEING RESEARCH REVIEWS

Investigational BACE inhibitors for the treatment of Alzheimer’s disease

(2019) Bruno P. Imbimbo et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Minocycline at 2 Different Dosages vs Placebo for Patients With Mild Alzheimer Disease

(2019) Robert Howard et al.   JAMA Neurology

Systematic review of the efficacy of statins for the treatment of Alzheimer’s disease

(2018) Marta Mejías-Trueba et al.   CLINICAL MEDICINE

Neurotoxic reactive astrocytes are induced by activated microglia

(2017) Shane A. Liddelow et al.   NATURE

Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline

(2016) David J. Koss et al.   ACTA NEUROPATHOLOGICA

The amyloid hypothesis of Alzheimer's disease at 25 years

(2016) Dennis J Selkoe et al.   EMBO Molecular Medicine

Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of Alzheimer’s Disease

(2016) Paul B. Rosenberg et al.   JOURNAL OF ALZHEIMERS DISEASE

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

(2016) Jeff Sevigny et al.   NATURE

Early etiology of Alzheimer’s disease: tipping the balance toward autophagy or endosomal dysfunction?

(2015) Aleksandar Peric et al.   ACTA NEUROPATHOLOGICA

Clinical trial of an inhibitor of RAGE-A  interactions in Alzheimer disease

(2014) D. Galasko et al.   NEUROLOGY

Amyloid-β and Tau

(2014) George S. Bloom   JAMA Neurology

A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease

(2013) Rachelle S. Doody et al.   NEW ENGLAND JOURNAL OF MEDICINE

Structural and Functional Brain Networks: From Connections to Cognition

(2013) H.-J. Park et al.   SCIENCE

Large-scale brain networks in cognition: emerging methods and principles

(2010) Steven L. Bressler et al.   TRENDS IN COGNITIVE SCIENCES

Complex brain networks: graph theoretical analysis of structural and functional systems

(2009) Ed Bullmore et al.   NATURE REVIEWS NEUROSCIENCE

Impaired insulin secretion increases the risk of Alzheimer disease

(2008) E. Ronnemaa et al.   NEUROLOGY