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Abstract Background This article reports a rare case of active neurosyphilis in a man with mild to moderate dementia and marked hippocampal atrophy, mimicking early onset Alzheimer’s disease. Few cases have so far described bilateral hippocampal atrophy mimicking Alzheimer’s disease in neurosyphilis. Case presentation The patient presented here is a 33 year old Bulgarian male, whose clinical features include progressive cognitive decline and behavioral changes over the last 18 months. Neuropsychological examination revealed mild to moderate dementia (Mini Mental State Examination score was 16/30) with impaired memory and attention, and executive dysfunction. Pyramidal, and extrapyramidal signs, as well as dysarthria and impairment in coordination, were documented. Brain magnetic resonance imaging showed cortical atrophy with noticeable bilateral hippocampal atrophy. The diagnosis of active neurosyphilis was based on positive results of the Venereal Disease Research Laboratory test/Treponema pallidum hemagglutination reactions in blood and cerebrospinal fluid samples. In addition, cerebrospinal fluid analysis showed pleocytosis and elevated protein levels. High-dose intravenous penicillin therapy was administered. At 6 month follow up, improvements were noted clinically, on neuropsychological examinations, and in cerebrospinal fluid samples. Conclusion This case underlines the importance of early diagnosis of neurosyphilis. The results suggest that neurosyphilis should be considered when magnetic resonance imaging results indicate mesiotemporal abnormalities and hippocampal atrophy. Neurosyphilis is a treatable condition which requires early aggressive antibiotic therapy.