BOX 1. TRANSLATIONAL CONCERNS WITH

BOX 1. TRANSLATIONAL CONCERNS WITH ANIMAL MODELS† There is lack of concordance between preclinical models and human clinical trials.– Potential reasons: wrong targets, incomplete models, lack of variability among individuals inthe models, patients enrolled too late, comorbidities† Humans enrolled in clinical trials are heterogenous,whereas most models utilize in-bred stains onmice.– Potential solution: evaluating novel treatments in multiple lines may help address this point† There is lack of substantial cell and synaptic loss in the majority of rodent models, suggesting themodels better represent the prodromal phase of the disease.† Models are of familial AD, and most people have sporadic AD.

BOX WITH ANIMAL MODELS 1. Concerns Translational
† There is Lack of concordance between preclinical models and clinical Human Trials.
- Potential Reasons: Wrong targets, incomplete models, Lack of variability among individuals in
the models, Patients Enrolled Too Late, comorbidities
† Enrolled Humans. in clinical Trials are heterogenous, whereas Most models utilize in-bred stains on
mice.
- Potential Solution: evaluating novel treatments in multiple Lines May help address this Point
† There is Lack of substantial Cell and synaptic loss in the majority of rodent models, suggesting. the
models better represent the prodromal phase of the disease.
† Models are of familial AD, and Most people have sporadic AD.

BOX 1. TRANSLATIONAL CONCERNS WITH ANIMAL MODELS
video There is lack of concordance between preclinical models and human clinical. Trials.
- Potential reasons: wrong targets incomplete, of, models lack variability among individuals in
the models patients,, Enrolled too late comorbidities
video, Humans enrolled in clinical trials are heterogenous whereas most, models utilize in-bred. Stains mice on
.
.To Potential solution: evaluating novel treatments in multiple lines may help address this point
video There is lack of substantial. Cell and synaptic loss in the majority of, rodent models suggesting the
models better represent the prodromal phase of the. Disease.
video Models are of familial AD and most, people have sporadic AD.