Background: Immunotherapy for Alzheimer’s disease(AD) has gained momentum in recent years. One of the concerns over its application pertains to Cost-Effectiveness Analysis (CEA) from population average and specific subgroup differences, as such a therapy is imperative for health decision-makers to allocate limited resources. However, this sort of CEA model considering heterogeneous population with risk factors adjustment has been rarely addressed. Methods: We aimed to show the heterogeneity of CEA in immunotherapy for AD in comparison with the comparator without intervention. Economic evaluation was performed via incremental Cost-Effectiveness Ratio (ICER) and Cost-Effectiveness Acceptability Curve (CEAC) in terms of the Quality-Adjusted Life Years (QALY). First, population-average CEA was performed with and without adjustment for age and gender. Secondly, sub-group CEA was performed with the stratification of gender and age based on Markov process. Results: Given the threshold of $20,000 of willingness to pay, the results of ICER without and with adjustment for age and gender revealed similar results ($14,691/QALY and $17,604/QALY). The sub-group ICER results by different age groups and gender showed substantial differences. The CEAC showed that the probability of being cost-effective was only 48.8%-53.3% in terms of QALY at population level but varied from 83.5% in women aged 50-64 years, following women aged 65-74 years and decreased to 0.2% in men≥ 75 years. Conclusion: There were considerable heterogeneities observed in the CEA of vaccination for AD. As with the development of personalized medicine, the CEA results assessed by health decision-maker should not only be considered by population-average level but also specific sub-group levels.