Neurodegenerative Alzheimer's Disease and Amyotrophic Lateral Sclerosis (NADALS) Basket Trial

Study participants meeting all of the following criteria will be allowed to enroll in the study:

1. Must be 55-90 years old, inclusive and have one of the following:

Must be 18-80 years old, inclusive and have one of the following:

2. Screening CSF level of CCL2 level ≥ 250 pg/mL

3. Up-to-date immunization records per CDC guidelines

4. Must have received the Recombinant Zoster Vaccine (RZV, also known as Shingrix) within 4 years prior to enrollment. Note: Only one dose of RZV is needed prior to the Baseline Visit.

5. Must be fully vaccinated for COVID-19 per CDC guidelines

6. For participants with ALS:

For participants with AD:

7. Ability to medically undergo LP in the opinion of the investigator (e.g., no bleeding disorder, allergy to local anesthetics, prior lumbar surgery which might make LP difficult, a skin infection at or near the LP site, evidence of high intracranial pressure, or anticipated difficulty getting into position for LP).

8. Capable of providing informed consent and following study procedures.

Study participants meeting any of the following criteria during screening evaluations will be excluded from entry into the study:

1. Women who are pregnant, breastfeeding, or planning to become pregnant during the trial

2. Any unstable clinically significant medical condition other than ALS or AD (e.g., within six months of baseline, including but not limited to myocardial infarction, angina pectoris, congestive heart failure, or neoplasm undergoing active treatment).

3. Active cancer or history of cancer, except for the following: basal cell carcinoma, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 5 years. Active cancer includes cancers with current disease manifestations or therapy that could adversely affect participant safety and longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.

4. History of diverticulitis or bowel perforation.

5. Active ulcerative colitis, Crohn's disease, and history of peptic ulcer disease within the past 5 years or after the age of 65.

6. Active, serious infection, including localized infection in the opinion of the investigator.

7. Positive for latent or active tuberculosis (TB). Note: Patients with a history of latent or active TB must have had an adequate course of treatment documented prior to study participation.

8. Evidence of active hepatitis B or C infection.

9. History of severe hepatic or renal impairment.

10. eGFR < 60 mL/min/1.73 m2

11. Have any of the following specific abnormalities on screening laboratory tests:

12. Personal history of pulmonary embolus (provoked or unprovoked) or deep vein thrombosis, or a history of unprovoked pulmonary embolus in a first-degree family member.

13. Treatment with anticoagulants that, in the opinion of the investigator, would compromise the safety of the participant.

14. Previous therapy with baricitinib.

15. Current use of strong Organic Anion Transporter 3(OAT3) inhibitors (e.g., probenecid) or other prohibited medication (refer to Section 6.7.1) within 5.5 half-lives or 30 days of screening, whichever is longer.

16. Receiving other experimental interventions for AD or ALS within 5.5 half-lives or 30 days of screening, whichever is longer.

17. Use of permanent assisted ventilation (invasive ventilation via tracheostomy, or >22 hours of non-invasive ventilation per day, e.g., via BiPAP).

18. Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator, would pose an unacceptable risk to the patient. Note: Placement of a gastrostomy tube and an intravenous port are not considered major surgery.