Neuron Number in the Entorhinal Cortex and CA1 in Preclinical Alzheimer Disease

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Abstract
SEVERAL clinicopathologic studies of older adults with slight cognitive decline before death, just at the threshold for clinical detection, demonstrated large numbers of neurofibrillary tangles and amyloid plaques, sufficient for the diagnosis of Alzheimer disease (AD).1-8 Reasoning that these pathological lesions develop over time, the pathobiological processes that underlie AD must begin in a preclinical stage that precedes clinically detectable cognitive change, probably by years. This preclinical AD stage would be a critical target for therapeutic intervention.