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Does a truly hippocampal sparing subtype of Alzheimer’s disease really exist?

The field of biological subtypes of Alzheimer’s disease (AD) has recently gained attention as a strong driver of precision medicine and future clinical trials. Neuropathology and neuroimaging studies have consistently identified four subtypes: hippocampal sparing AD, typical AD, limbic predominant AD, and minimal atrophy or minimal tau NFT AD. An important and still unresolved question is whether a truly hippocampal sparing subtype of AD can really exist, since it would challenge the widely accepted model of NFT spread. To address this question, we conducted a systematic review of the literature and performed original analyses on tau PET data.