Peripheral neuropathy as a presenting feature of familial early onset Alzheimer’s disease: a rare clinical association

AI Summary

Sensory peripheral neuropathy preceded cognitive decline by almost a decade in a genetically confirmed familial early-onset Alzheimer's patient.
Genetic testing identified heterozygous PSEN1 c.349 C>T (p.Pro117Ser) mutation in exon 5 associated with the clinical course.
The report emphasises rarity of this association and recommends thorough clinical and electrophysiological evaluation for sensory symptoms in such patients.

AI Summary

We describe a patient with genetically confirmed familial early-onset Alzheimer's disease in whom sensory peripheral neuropathy preceded cognitive decline by almost a decade.

To the best of our knowledge, peripheral neuropathy as an initial manifestation of familial early-onset Alzheimer's disease has never been reported before and could be a possible manifestation of the underlying degenerative process.

With this report, we highlight the rarity of this association and underscore the importance of a comprehensive clinical and electrophysiological evaluation in patients with familial early-onset Alzheimer's disease who present with sensory symptoms, gait disturbances, skin or trophic changes, or other clinical features suggestive of peripheral neuropathy.

Basic summary

Acta Neurol Belg. 2026 Jul 10. doi: 10.1007/s13760-026-03142-5. Online ahead of print.

ABSTRACT

We describe a patient with genetically confirmed familial early-onset Alzheimer’s disease in whom sensory peripheral neuropathy preceded cognitive decline by almost a decade. A 40- year- old man presented with clinical and electrophysiological features of sensory neuropathy, and 9 years later developed memory disturbances. Genetic testing revealed a heterozygous PSEN1 c.349 C > T (p. Pro117Ser) mutation in exon 5. To the best of our knowledge, peripheral neuropathy as an initial manifestation of familial early-onset Alzheimer’s disease has never been reported before and could be a possible manifestation of the underlying degenerative process. With this report, we highlight the rarity of this association and underscore the importance of a comprehensive clinical and electrophysiological evaluation in patients with familial early-onset Alzheimer’s disease who present with sensory symptoms, gait disturbances, skin or trophic changes, or other clinical features suggestive of peripheral neuropathy.

PMID:42426493 | DOI:10.1007/s13760-026-03142-5

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