Recently, early diagnosis of Alzheimer’s disease (AD) has attracted considerable attention in the field of nanomedicine and biosensing. In particular, detection of plasma biomarkers specific for AD, including amyloid beta (Aβ40 and Aβ42), is considered a promising, cost-effective, and non-invasive method for diagnosis of AD. Herein, we present a facile approach for designing a nanoprobe based on surface-enhanced Raman scattering (SERS) for the sensitive and selective detection of Aβ40 and Aβ42 in blood. To this end, Ag nanoshells (AgNSs) bearing Raman labels were synthesized in a single step under very mild conditions (25 oC and 60 min). As-prepared AgNSs had a uniform shell thickness and nanogaps of 2 nm, resulting in significant electromagnetic field enhancement. In addition, each AgNS exhibited a unique and intense SERS signal without overlapping, allowing the multiplex and sensitive detection of Aβ40 and Aβ42. The AgNSs conjugated with a specific antibody for Aβ40 or Aβ42 was able to detect each target protein at concentration as low as 100 fg/ml in a fast and simple manner.