Age-related clinical heterogeneity in severe Alzheimer’s disease


  • Patients with early onset Alzheimer’s disease (EOAD), especially those without the (Apolipoprotein E) APOE ɛ4 AD risk allele, are more likely to report atypical symptoms which may be misattributed to non-AD pathology.

Why this matters

  • The clinical and neuropathologic presentation of AD is dependent on age-related heterogeneity but, as many studies did not include autopsy verification, it is not known how this heterogeneity relates to the typical AD pathology, non-AD pathology or non-AD pathology superimposed on AD.

  • Compared with the late onset AD (LOAD), EOAD is characterized by atypical presentations (faster cognitive decline, less prominent memory impairment and a higher incidence of focal cortical syndromes), which are particularly common in the absence of the APOE ɛ4 AD risk allele. 

  • This study investigated age-related clinical heterogeneity of AD to determine its relationship with APOE genotype and non-AD pathology.